PhD students from all years of the program are invited to present their research through an oral presentation or a poster. Abstracts are sorted by presentation type, and further sorted by field.
Biological and Biomedical
Establishing the transient mass balance of thrombosis under flow
Jason Chen, Scott L. Diamond
AbstractCoagulation kinetics are well established in well plates assays in which human plasma clots isotropically. However, less is known about thrombin kinetics and transport within clots formed under hemodynamic flow. Understanding these processes and how they are regulated is of major medical importance. Using microfluidic perfusion of Factor XIIa-inhibited human whole blood (200 s-1 wall shear rate) over a 250-micron long patch of collagen/tissue factor (~1 TF molecule/μm2) and immunoassays of the effluent for fragment 1.2 (F1.2), thrombin-antithrombin (TAT), and D-dimer (post-endpoint plasmin digest), we sought to establish the transient mass balance for clotting under venous flow. Based upon these measurements under flow condition, we have developed a reduced model of clotting. Using a thin film approximation, we were able to simplify clotting under flow to 8 ODEs and 19 kinetic and stoichiometric parameters. A total of 16 parameters were from literature and only 3 needed adjustment in order to fit the measured thrombin generation (TAT and F1.2) and fibrin generation data. The model required fibrinogen penetration into the clot to be strongly diffusion-limited (actual rate/ideal rate = 0.05), which is not unexpected given the size of fibrinogen. The model required free thrombin in the clot (~100 nM) to have an elution half-life of ~2 sec, consistent with measured albumin elution, with most thrombin (>99%) being fibrin-bound. Thrombin-feedback activation of FXIa became prominent and reached 5 pM at >500 sec in the simulation, consistent with anti-FXIa experiments. In a full convection/diffusion simulation, the velocity field and convective-diffusive transport solved by COMSOL and indicated that binding of thrombin onto fibrin was strong under venous shear rate with an apparent half-life in the clot of 1.1 hour. To sum up, our reduced model, which supported by experimental data, predicts thrombin and fibrin co-regulation during thrombosis under flow, gives insights into the dynamics of the species involved and may be useful for multiscale simulation.
Effect of patterning of ICAM-1 on the Upstream Migration of CD4+ T-Cells Under Shear Flow
Adam B. Suppes and Daniel A. Hammer
AbstractRecently it has been shown that some leukocyte cell types, including activated primary CD4+ T-cells, can migrate upstream under shear flow after arrest on ICAM-1, Intercellular Adhesion Molecule 1. CD4+ T-cells do not express this behavior on VCAM-1, Vascular Cellular Adhesion Molecule 1. By combining ICAM-1 and VCAM-1 on a surface, we have shown that any amount of ICAM-1 supports upstream migration. The objective of this study was to determine if the patterning of ICAM-1 and VCAM-1 into stripes and patterns had any influence on the direction of T-cell migration.
Primary CD4+ cells were seeded onto four types of patterned surfaces. Two PDMS stamp archetypes were utilized; Uniform stamps provide an even distribution of adhesion proteins on the slide and striped stamps print the adhesion proteins in stripes of 50, 100, or 200 μm width with the equivalent spacing between stripes. Experiments were performed an equal mass mixture of ICAM-1 and VCAM-1. In addition, three flow conditions were chosen: static, a shear rate of 400 s-1, and a shear rate of 800 s-1. We show that on uniform surfaces, T-cells migrate upstream, consistent with previous results. As a control, no directional migration was seen on these surfaces under static conditions. On 50μm wide stripes oriented parallel to the flow, CD4+ T-cells migrate downstream under shear flow, rather than upstream as observed on the uniform surfaces. Widening the stripe to 100μm does not reestablish upstream migration, but rather led to migration that was not statistically different than random migration. On surfaces with 200μm stripes, upstream migration is re-established.
Scaling concepts in ’omics: nuclear lamin-B scales with tumor growth and predicts poor prognosis, whereas fibrosis can be pro-survival
Manasvita Vashisth, Sangkyun Cho, Jerome Irianto, Yuntao Xia, Mai Wang, Brandon Hayes, Farshid Jafarpour, Rebecca Wells, Andrea Liu, and Dennis E. Discher
AbstractSpatiotemporal relationships between genes expressed in tissues likely reflect physicochemical principles that range from stoichiometric interactions to co-organized fractals with characteristic scaling. For key structural factors within the nucleus and extracellular matrix (ECM), gene-gene power laws are found to be characteristic across several tumor types in The Cancer Genome Atlas (TCGA) and across single-cell RNA-seq data. The nuclear filament LMNB1 scales with many tumor-elevated proliferation genes that predict poor survival in 9 primary tumors, and cell line experiments show LMNB1 regulates cancer cell cycle. Moreover, transcription factor FOXM1 that has putative binding sites on the promotor region of LMNB1, scales with LMNB1 for 20 primary tumors. Fibrosis-associated collagens, COL1A1 and COL1A2, that scale stoichiometrically with each other and superstoichiometrically with a pan-cancer fibrosis gene set. However, high fibrosis predicts prolonged survival of patients undergoing therapy and does not correlate with LMNB1 in liver cancer. Single-cell RNA-seq data also reveal scaling consistent with the pan-cancer power laws obtained from bulk tissue, allowing new power law relations to be predicted. Lastly, although noisy data frustrate weak scaling, concepts such as stoichiometric scaling highlight a simple, internal consistency check to qualify expression data.
Energy and Catalysis
Dehydra-decyclization of tetrahydrofurans to diene monomers over metal oxides
Yichen Ji, Ajibola Lawal, Andrew Nyholm, Omar A. Abdelrahman, Raymond J. Gorte
AbstractThe dehydra-decyclization of tetrahydrofuran (THF) to butadiene was investigated over a series of metal oxide catalysts, where a common set of chemical pathways was identified. Alongside butadiene, propene is formed via a retro-Prins condensation as the main side product typically observed. Reaction occurred at similar temperatures on each of the oxides, but tetragonal zirconia (t-ZrO2) and monoclinic zirconia (m-ZrO2) were unique in showing high selectivity to butadiene (>90%). Near quantitative yields to butadiene could be achieved over t-ZrO2 at 673 K and a WHSV of 0.93 g THF gcat−1 h−1. Through contact time studies, butadiene is determined to be a primary product. Methyl-substituted THF gave only moderate increases in rates and the products showed minimal isomerization of the carbon backbone. The t-ZrO2 catalyst was found to be relatively stable with time on stream, experiencing coking as a likely source of deactivation. Complete regeneration of the catalyst was demonstrated through calcination alone, allowing for multiple regenerations with no irreversible loss in activity or selectivity. The catalytic activity of zirconia was found to be structure insensitive, with t-ZrO2 and m-ZrO2 exhibiting similar initial activities; however, m-ZrO2 was observed to deactivate much more rapidly.
Computational Study of Tuned 2D MXene Materials as New Age Catalysts through First Principle Calculations and Data Driven Discovery
Luke Johnson, Aleksandra Vojvodic
AbstractDiscovering materials with cheap and abundant elements, tunable properties, activity at ambient conditions, and late transition metal-like chemical activity is crucial in advancing the hydrogen economy and sustainable ammonia synthesis. While the Haber-Bosch process is the most important invention of the 20th century, it has energy intensive conditions and massive CO2 output. One possible way to tackle this involves using ambient nitrogen to produce ammonia electrochemically. Unfortunately, one of the key limitations of standard metal catalysts is overcoming the competing hydrogen evolution reaction. Due to the large amount of existing catalytic data, learning methods have been used to predict and infer chemical and physical properties through analyzing datasets and building atomistic potentials. My research involves exploring a new class of materials through first principle methods for their nitrogen and hydrogen reduction activities through use of first principles calculations and fundamental catalysis.
This presentation will cover three aspects of my research in this search for activity tuning parameters. The first part of my research involves performing high-throughput computational screening on 65 functionalized 2D MXene materials to investigate their activity for the electrochemical nitrogen reduction. It was discovered that great variation existed in the energy pathway as a function of the non-metal component, metal constituent, and the functionalization group of the MXene. Based on this analysis, a single H-functionalized MXene was identified as a potential candidate based on its stability and activity. The second part of my research attempts to capture the compositional and structural effects of sulfur modifications to twelve distinct Mo- and Ti-based 2D MXene materials on their stability and activity for catalyzing the hydrogen evolution reaction (HER). The explored modifications include geometric, stoichiometric, and structural changes via S doping and/or strain/support effects to compare with experimentally synthesized S-treated MXenes. We identified a direct relationship between hydrogen adsorption energy and the S atomic composition of the MXenes. Finally, we take the generated catalytic data from the previous studies and applies advanced techniques to understand and make this data useful. Using machine learning methods from linear regression to random forest bagging, it was determined that the reactivity of intermediates on the surface is highly dependent on the type of surface termination and the symmetry of the adsorbate.
This work provides not only invaluable data to the 2D materials and catalysis communities but crucial analyses and fundamental understanding into how we can design materials and substances with high chemical activity through altering their electronic structure. The study also extends as a guideline to the scientific community on how to treat structured data in an appropriate manner to extract crucial insights needed to design new systems and improve upon existing ones.
Investigation of Rh-titanate (ATiO3) interactions on high-surface-area perovskites thin films prepared by atomic layer deposition
Chao Lin, Alexandre C. Foucher, Yichen Ji, Eric A. Stach & Raymond J. Gorte
AbstractThin, ~1-nm films of CaTiO3, SrTiO3, and BaTiO3 were deposited onto MgAl2O4 by Atomic Layer Deposition (ALD) and studied as catalyst supports for Rh. Scanning Transmission Electron Microcopy (STEM) and X-Ray Diffraction (XRD) demonstrated that the films had the perovskite structure and formed uniform coatings stable to 1073 K. Rh, added by ALD, interacted strongly with CaTiO3 and somewhat less strongly with SrTiO3, while Rh on BaTiO3 was similar to Rh on unmodified MgAl2O4. STEM measurements of Rh on CaTiO3 films showed Rh remained well dispersed after repeated oxidations and reductions at 1073 K; however, the Rh was inactive for CO-oxidation. Rh formed small particles on SrTiO3 films and was active for CO oxidation after reduction at 1073 K. The reducibility and catalytic activity of Rh/BaTiO3/MgAl2O4 were similar to that of Rh/MgAl2O4. Evidence from CO-TPR, FTIR, and XPS all indicated that the degree of interaction between Rh and the three perovskite films can be ranked in the following order: Rh/CaTiO3/MgAl2O4 > Rh/SrTiO3/MgAl2O4 > Rh/BaTiO3/MgAl2O4. Bulk ex-solution catalysts, synthesized by reduction of ATi0.98Rh0.02O3 (A=Ca, Sr, and Ba), were also examined for comparison.
Designing catalysts for electrochemical water-splitting: A first-principles approach
Abhinav S. Raman, Aleksandra Vojvodic
AbstractAchieving a sustainable energy future is the pressing need of the hour to combat the ever-increasing threat of climate change. Electrochemical water-splitting to produce hydrogen which can then be used directly as a fuel or for the sustainable production of valuable chemicals such as ammonia has been considered as a vital process in the sustainable energy puzzle. Despite considerable progress, electrochemical water-splitting is plagued by large overpotentials associated with the oxygen evolution reaction (OER), necessitating the use of rare-earth electrocatalysts such as Ru and Ir based oxides for improved activity. Additionally, the poor stability of these materials results in their low operational lifetimes, causing the well-known ‘activity-stability’ conundrum in water-splitting.1 To resolve this, we take a two-pronged approach based on first-principles methods. First, we present an approach to activate stable inert oxides by sub-surface doping to form hetero-structured oxides which show much enhanced activity for the OER, with the added advantage of utilizing a much lower content of rare-earth constituents.2 Next, we present an ab-initio thermodynamic framework for modeling the dissolution of highly active OER catalysts, providing a route to the atomistic understanding of the stability of these materials, with the aim of designing both stable and active electrocatalysts for water-splitting.3
Reference:
1.L. C. Seitz et al. Science 2016, 353, 1011-1014.
2.L. Zhang, A.S. Raman and A.Vojvodic, Chem. Mater. 2020, 32, 5569-5578.
3.A.S. Raman, R.Patel and A.Vojvodic, Accepted, Faraday Discuss. 2020.
Soft Matter
Nanoscale Thickness Control of Nanoporous Films Derived from Directionally Photopolymerized Mesophases
O. Qaboos Imran, Na Kyung Kim, Lauren Bodkin, Gregory Dwulet, Xunda Feng, Kohsuke Kawabata, Douglas Gin, Chinedum O. Osuji*
AbstractThe preparation of thin films of nanostructured functional materials is a critical step in a diverse array of applications ranging from photonics to separation science. New thin-film fabrication methods are sought to harness the emerging potential of self-assembled nanostructured materials as next-generation membranes. Here, we show that nm-scale control over the thickness of highly ordered self-assembled mesophases can be enacted by directional photopolymerization in the presence of highly attenuating molecular species. Metrology reveals average film growth rates below ten nanometers per second, indicating the high-resolution fine-tuned film fabrication possible with this approach. The trends in experimental data are reproduced well in simulations of mean-field frontal photopolymerization modeled in a highly attenuating photobleaching media, thereby connecting the measured high-resolution film growth rates to the highly attenuating nature of the mesophase resulting from its high aromatic-ring content. Water permeability measurements of the fabricated thin-films show the expected scaling of permeability with film thickness and permeabilities compare favorably with current state-of-art Nanofiltration and Reverse Osmosis membranes.
Effects of intermolecular interactions and internal degrees of freedom in simulated vapor deposited glass films
Alex Moore, Shivagee Govind, Aixi Zhang, Yi Jin, Patrick Walsh, Zahra Fakhraai , Robert Riggleman
AbstractRecently, amorphous films of small molecules formed via physical vapor deposition (PVD) have been shown to exhibit remarkable thermodynamic and kinetic properties, equivalent to those that have been aged for time scales on the order of hundreds of years. Previous experiments and simulations suggest that the stability differences observed in these PVD glass films are the result of enhanced mobility near the free surface, such that molecules are allowed to sample a greater number of configurations before becoming trapped by subsequent deposited layers. However, much remains to be learned about the effects of properties like molecular composition and rotational freedom on the stability and morphology of these PVD amorphous packings. By using molecular dynamics simulations to mimic the PVD process of coarse-grained small molecules, we can make fine-tuned changes to these properties and then closely observe changes in films, both during and after the deposition process. Notably, we can then make a connection between changes in intermolecular interactions and internal degrees of freedom and the corresponding changes in molecular mobility, excess entropy, and PVD film properties.
Dimerization and structure formation of colloids via capillarity at curved fluid interfaces
Alismari Read, Sreeja Kutti Kandy, Iris B Liu, Ravi Radhakrishan, Kathleen Stebe
AbstractStructures made by colloidal particles adsorbed at the interface of two immiscible fluids have broad practical significance. For example colloids at interfaces are used to stabilize emulsions in diverse fields including pharmaceuticals and personal care, and are also used to form mesostructures in advanced materials. Colloids are known to accumulate and organize at fluid interfaces via capillary interactions. When a particle is adsorbed at a fluid interface, it distorts the surrounding interface, increasing its area. The product of surface tension and this area is the capillary energy. When the distortions between two particles overlap, the interfacial area decreases, and particles attract minimizing the free energy of the system. On curved interfaces, capillary interactions direct isolated colloid motion along deviatoric curvature gradients. This directed motion relies on the leading order, long-ranged quadrupolar distortions made by the colloids’ undulated pinned contact lines.
In this work we study pair interactions and dimer formation of colloids on interfaces with well-defined curvature fields using particle-tracking methods. Since the particles move in creeping flow, analysis of particle trajectories allows the energy of interaction to be inferred. We have formulated a theoretical analysis to find the interaction energy of two particles on the curved interface. Interestingly, the distortion made around even spherical colloids is highly anisotropic because of contact line pinning on high-energy sites where the interface intersects the particles. Because of this broken symmetry, for dimers, the energy is minimized when the line of centers align along the principal axes of the interface; this is seen in experiment and predicted by theory. We have used this pair potential in Monte Carlo simulation to understand structures formed by multiple particles. Again, particular alignments between the particle line of centers are evident in the assemblies, which differ significantly from structures formed via other mechanisms, for example simple diffusion limited aggregation. This fundamental study provides insights to directed assembly using interface shape, and shows the remarkable importance of geometry in resulting particle structures.
pH mediated nanoparticle dynamics in silica-polyacrylamide hydrogels
Katie A. Rose, Daeyeon Lee, Russell J. Composto
AbstractThe effect of a tertiary component of nanoparticle (NP) probe diffusion in hydrogels was investigated through the addition of silica particles (0% – 10% volume) in polyacrylamide hydrogels using single particle tracking (SPT). Low concentrations of homogenously dispersed silica (0.5% volume) created two distinctive populations of diffusing NPs, localized and mobile, compared to the neat hydrogel. A proposed mechanism for the localized behavior of the NP probes is the pH mediated attraction between the PEG brush of the nanoparticle probe and the surface of the silica particle. Using quartz crystal microbalance with dissipation (QCM-D), the extent of this interaction at different pHs was investigated. At pH 5.8, the PEG brush on the NPs probes are capable of hydrogen bonding with the surface of the silica, leading to absorption of the NPs onto a silica coated crystal. At pH 9.2, the surface of the silica is protonated, and the PEG brush of the NPs are unable to hydrogen bond with the surface of the silica, leading to negligible absorption. The effect of pH on NP dynamics in silica incorporated polyacrylamide gels has been further investigated with SPT for 0.5% volume silica-polyacrylamide hydrogels at pH 5.8 and pH 9.2. This study of NP dynamics provides insight into controlling the dynamics of NPs in hydrogels based on pH mediated interactions with an incorporated tertiary component, with implications in drug delivery and filtration.
Dynamical Decomposition in Model Polymer Nanocomposites under Creep
Entao Yang, James Pressly, Bharath Natarajan, Aruna Mohan, Karen Winey, Robert Riggleman
AbstractWhile the elastic properties of polymer nanocomposites (PNCs) have been widely studied, the ability of nanoparticles (NPs) to suppress creep in a polymer matrix has received comparatively less attention. The presence of a slow-dynamic layer near NPs’ surface is widely believed to be the primary mechanism of NPs’ reinforcement. Thus, understanding how the interfacial dynamics, structures, and creep response change as a function of stress, NP size, and polymer-NP interactions is critical. Here, by introducing a ratio of the interfacial dynamics to the bulk dynamics, we decompose the dynamics in PNCs into two parts: one that is structure-dependent as indicated by the local softness, and a second that is structure-independent. Also, with this decomposition, particles’ free energy barrier for rearrangement can be described as a combination of a local barrier (packing related) and a long-range barrier (packing unrelated). We prove that our decomposition can be further expanded to PNCs undergoing linear creep, where both barriers are higher near NPs and decrease with increasing stress, and the structure-independent energy barrier is much larger than the local one.
Directed Assembly and Micromanipulation of Passive Colloids in Nematic Liquid Crystals
Tianyi Yao, Yimin Luo, Daniel A. Beller, Francesca Serra, and Kathleen J. Stebe
AbstractNematic liquid crystals (NLCs) offer remarkable opportunities to direct colloids to form complex structures. The elastic energy field that dictates colloid interactions is determined by the NLC director field, which is sensitive to and can be controlled by boundaries including vessel walls and colloid surfaces. By molding the director field via liquid-crystal alignment on these surfaces, elastic energy landscapes can be defined to drive structure formation. We focus on homeotropic colloids in NLC director fields formed near undulating walls and magnetic microrobots of desired geometries. Colloids can be driven along prescribed paths and directed to well-defined docking sites on such wavy boundaries. Colloids that impose strong alignment generate topologically required companion defects. Configurations for homeotropic colloids include a dipolar structure formed by the colloid and its companion hedgehog defect or a quadrupolar structure formed by the colloid and its companion Saturn ring. Adjacent to solid boundaries with wavelengths larger than the colloid diameter, colloids are attracted to locations with distortions in the nematic director field that complement those from the colloid. This is the basis of lock-and-key interactions. Here, we study both isotropic and anisotropic colloids with homeotropic anchoring near complex undulating walls and magnetic microrobots. The boundaries impose distortions that decay with distance from the solid surfaces to a uniform director in the bulk. Directed assembly of passive colloids is achieved near undulating walls with compatible geometries. Furthermore, manipulation of colloids in bulk NLC is demonstrated using a magnetic microrobot.
Biological and Biomedical
Thermal shift assay to probe melting of thrombin, fibrinogen, fibrin monomer, and fibrin: Gly-Pro-Arg-Pro induces a fibrin monomer-like state in fibrinogen
Jennifer Crossen, Scott L. Diamond
AbstractThrombin activates fibrinogen and binds the fibrin E-domain (Kd ~ 2.8 μM) and the splice variant γ’-domain (Kd ~ 0.1 μM). We investigated if the loading of D-Phe-Pro-Arg-chloromethylketone inhibited thrombin (PPACK-thrombin) onto fibrin could enhance fibrin stability. A 384-well plate thermal shift assay (TSA) with SYPRO-orange provided melting temperatures (Tm) of thrombin, PPACK-thrombin, fibrinogen, fibrin monomer, and fibrin. As indicated by large increases in Tm, calcium led to protein stabilization (0 vs. 2 mM Ca2+) for fibrinogen (54.0 vs. 62.3 °C) and fibrin (62.3 vs. 72.2 °C). As expected, fibrin was more stable than fibrinogen (+ Ca2+). Additionally, active site inhibition with PPACK dramatically increased the Tm of thrombin (58.3 vs. 78.3 °C). Treatment of fibrinogen with fibrin polymerization inhibitor GPRP increased fibrinogen stability by ΔTm = 9.3 °C, similar to the ΔTm when fibrinogen was converted to fibrin monomer (ΔTm= 8.8 °C) or to fibrin (ΔTm = 10.4 °C). Addition of PPACK-thrombin at high 5:1 molar ratio to fibrin (or fibrinogen) had little effect on fibrinogen or fibrin Tm values, indicating that thrombin binding does not detectably stabilize fibrin via a putative bivalent E-domain to γ’-domain interaction. TSA was a sensitive assay of protein stability and detected: (1) the effects of calcium-stabilization, (2) thrombin active site labeling, (3) fibrinogen conversion to fibrin, and (4) GPRP induced changes in fibrinogen stability being essentially equivalent to that of fibrin monomer or polymerized fibrin.
Core and shell platelets of a thrombus: A new microfluidic assay to study mechanics and biochemistry
Michael DeCortin, L.F. Brass, Scott L. Diamond
AbstractA 2-stage assay perfused whole blood over collagen/± tissue factor (TF) for 180 seconds at 100 s−1 wall shear rate followed by buffer perfusion at either 100 s−1 (venous) or 1000 s−1 (arterial). This microfluidic assay used an extended channel height (120 μm), allowing buffer perfusion well before occlusion. Clot growth on collagen stopped immediately with buffer exchange, revealing ~10% reduction in platelet fluorescence intensity (at 100 s−1) and ~30% (at 1000 s−1) by 1200 seconds. Thrombin generation (on collagen/TF) reduced erosion at either buffer flow rate. P-selectin positive platelets were stable (no erosion) against 1000 s−1, in contrast to P-selectin negative platelets. Thrombin inhibition (with D-Phe-Pro-Arg-CMK) reduced the number of P-selectin positive platelets and lowered thrombus stability through the reduction of P-selectin positive platelets. Interestingly, fibrin inhibition (with H-Gly-Pro-Arg-Pro-OH acetate salt) increased the number of P-selectin positive platelets but did not lower stability, suggesting that fibrin was only in the core region. Thromboxane inhibition reduced P-selectin positive platelets and caused a nearly 60% reduction of the clot at arterial buffer flow. P2Y1 antagonism reduced clot size and the number of P-selectin positive platelets and reduced the stability of P-selectin negative platelets. The 2-stage assay (extended channel height plus buffer exchange) interrogated platelet stability using human blood. Under all conditions, P-selectin positive platelets never left the clot.
Dynamic gene control through interallelic interactions in Drosophila embryos
Hao(Dennis) Deng, Bomyi Lim
AbstractThe mechanism of which enhancers interact with the target promoter to initiation transcription has been extensively studied. However, recent studies suggest that 3D genome organization also plays an important role in gene regulation. We use live-imaging methods and quantitative analysis in living Drosophila embryos to show that interallelic interactions can affect transcriptional dynamics. We show that reporter genes at homologous position interfere with each another, resulting in reduced mRNA production from each allele. Such interference was not observed when the reporter genes were positioned at non-homologous locations.
Interestingly, we find that homologous alleles interfere with each other when one allele has only a partial transcription unit (enhancer only or a promoter-reporter gene only without the cis-linked enhancer). We propose that the allelic interactions may occur through clusters of transcription factors and mediator+Pol II complexes, and the transcriptional machineries are shared between two alleles to result in reduced transcriptional activity.
Characterizing Hydrophilic Surface Patches on Proteins for Non-Fouling Surfaces
Lilia Escobedo, Nick Rego, Amish Patel, Daeyeon Lee
AbstractSurface contamination due to biofouling is a common problem in a wide variety of industries because it reduces the effectiveness of devices ranging from medical implants, filtration membranes, to biosensors. One of the biggest challenges in creating anti-biofouling surfaces is that proteins have a wide array of surface chemical patterns that allow them to adsorb easily to most surfaces via non-specific binding. Since biofouling often occurs in aqueous environments, one way to combat this binding is to increase a surface’s affinity to water by altering its surface chemistry through hydrophilic and/or zwitterionic coatings to enhance surface hydration. However, homogeneous surfaces are at an inherent disadvantage against fouling by proteins, which have a wide variety of chemistries at their disposal. To address this challenge, we seek inspiration from the surfaces of proteins, which have evolved to resist non-specific aggregation and fouling by other proteins in the crowded cellular environment. Using MD simulations and the DBSCAN clustering algorithm, we identify patches of similar hydrophilicity on the surfaces of various proteins. By characterizing the most hydrophilic patches, we aim to uncover the chemical patterns responsible for protein-protein selectivity and provide a basis for the creation of non-fouling surfaces.
CD4+ T lymphocytes migrate upstream on substrates with varying stiffness
Sarah Hyun Ji Kim, Daniel A. Hammer
AbstractCD4+ T lymphocytes interact with various cell types and tissue substrates in response to inflammation. Mechanotransduction in T lymphocytes are frequently studied at immunological synapses (IS) during T cell activation, with T cell receptors (TCR), costimulatory receptors (i.e. CD3/CD28) and LFA-1 integrins. However, studying mechanotaxis in the context of leukocyte recruitment in circulation is limited. In circulation, endothelial cells alter the expression of Intracellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) to recruit leukocytes. CD4+ T lymphocytes use LFA-1 and VLA-4 integrins to bind to ICAM-1 and VCAM-1, respectively, for strengthened adhesion and migration. Recently, in vitro and in vivo studies suggest T cells migrate upstream when (i.e. in the opposite direction of shear flow) mediated by LFA-1—ICAM-1 interaction. As CD4+ T lymphocytes respond to shear flow, we hypothesized that the dependence of upstream migration on a specific adhesive pathway suggests mechanotransduction is critical to migration. We have devised polyacrylamide gels with pre-determined stiffness and functionalized with ICAM-1 and VCAM-1 to investigate how substrate mechanics affect integrin-dependent motility of CD4+ T cells. Under static conditions, we found that T cells on ICAM-1 surfaces, forming LFA-1-ICAM-1 interactions, elicit stiffness-dependent motility, but not on VCAM-1 or 1:1 mixture of VCAM-1/ICAM-1 surfaces (mixed surfaces). With integrin subunit-specific blocking antibodies and soluble ligands, we further confirmed that the crosstalk of the two integrins, LFA-1 and VLA-4, displays increased motility, but is insensitive to substrate stiffness. Lastly, we observed that CD4+ T cells still migrate upstream under flow on hydrogels functionalized with ICAM-1, independent of substrate stiffness.
A 3D Multiscale Framework for Patient-Specific Prediction of Platelet Aggregation Under Flow
Kaushik N. Shankar, Scott L. Diamond, and Talid Sinno
AbstractAtherosclerotic plaque rupture exposes blood to a highly procoagulant surface containing tissue factor, causing platelets to become activated. Activated platelets release soluble agonists such as ADP and thromboxane, causing further activation and platelet recruitment, resulting in thrombus growth. In this work, we have extended our previous 2D multiscale model of thrombosis in a microfluidic channel to develop a fully spatially resolved 3D framework with capabilities to simulate patient-specific phenotypes. The multiscale framework is composed of four modules: Neural Network (NN), Lattice Kinetic Monte Carlo (LKMC), Lattice Boltzmann (LB) and Finite Volume Method (FVM). The NN module is patient-specific, and computes the time-dependent degree of platelet activation, as indicated by intra-platelet calcium concentration given agonist-exposure history for each platelet. The LKMC module is used to track platelet positions and perform platelet binding and unbinding events. The LB module is used to update the blood flow field which evolves due to platelet deposition. The FVM module tracks soluble agonist concentrations by solving the convection-diffusion-reaction equation. Thrombus growth dynamics and morphology predicted by the model agree well with experiments. Furthermore, the model is flexible and can accommodate a variety of simulation domains, such as stenoses and bifurcations. To our knowledge, our model is the first of its kind that accounts for individual platelet phenotypes to perform robust 3D simulations of thrombosis, facilitating the identification of patient-specific thrombotic risks and drug responses.
The role of c-MYC induced cellular reprogramming in mechanosensing and stress-response of cancerous cells
Reshma Kalyan Sundaram, Bomyi Lim, Ravi Radhakrishnan
AbstractAvian myelocytomatosis viral oncogene homolog codes for a transcription factor c-Myc (Myc) that regulates the expression of genes involved in multiple cellular processes such as cell adhesion, cell-cell communication, ribosome biogenesis, protein synthesis, and cell metabolism, making it a potent oncogene. Amplification of the MYC gene is commonly observed in various human cancer types. An individual cell’s stress response has previously been shown to depend on the mechanical factors in its microenvironment such as substrate stiffness. Myc activation causes cells to experience intrinsic stress, whereas extrinsic stress can be regulated by various factors such as cell shape and substrate stiffness. By analyzing sequencing data of a mouse-derived hepatocellular carcinoma cell line, EC4, under Myc-on/off conditions we have identified a specific subset of genes associated with cytoskeleton, microtubule, and integrin-binding that are regulated by Myc. It is noteworthy that substrate stiffness can (through the integrin-Rho-ROCK pathway) activate Myc, which in-turn modulates cell-substrate interactions through transcriptional regulation of genes in cytoskeletal and integrin binding processes, thereby creating a feedback loop for mechanosensing. Investigating the nature of this feedback loop could shed insight into how Myc potentiates the effect of extracellular matrix stiffness on cell response. Therefore, we plan to study the stress response of cancer cells under Myc-on/off conditions by varying the substrate stiffness. In our approach, we employ biophysical modeling to understand the regulation of Myc and its downstream targets, which will be used as a guide to design our future experiments. We expect that our results will shed insights into the role of Myc-potentiated mechanosensing in driving cellular transformation in cancer.
The nuclear to cytoplasmic ratio directly regulates zygotic transcription in Drosophila through multiple modalities
Sahla Syed, Henry Wilky, Amanda Amodeo, Bomyi Lim
AbstractEarly embryos must rapidly generate large numbers of cells to form an organism. Many species accomplish this through a series of rapid, reductive, and transcriptionally silent cleavage divisions. Previous work has demonstrated that the number of divisions before both cell cycle elongation and zygotic genome activation (ZGA) is regulated by the ratio of nuclear content to cytoplasm (N/C). To understand how the N/C ratio affects the timing of ZGA, we directly assayed the behavior of several previously identified N/C-ratio-dependent genes using the MS2-MCP reporter system in living Drosophila embryos with altered ploidy and cell cycle durations. For every gene that we examined, we found that nascent RNA output per cycle is delayed in haploid embryos. Moreover, we found that the N/C ratio influences transcription through three separate modes of action. For some genes (knirps and snail) the effect of ploidy can be entirely accounted for by changes in cell cycle duration. However, for other genes (giant, bottleneck and fruhstart) the N/C ratio directly affects ZGA. For giant and bottleneck, the N/C ratio regulates the kinetics of transcription activation, while for fruhstart it controls the probability of transcription initiation. Our data demonstrate that the regulatory elements of N/C-ratio- dependent genes respond directly to the N/C ratio, through multiple modes of regulation, independent of interphase length.
Fibrin Attenuates Sorting of Phosphatidylserine Exposing Platelets During Clotting Under Flow
Kevin T. Trigani, Scott L. Diamond
AbstractAs thrombosis proceeds, certain platelets in a clot expose phosphatidylserine (PS) on their outer membrane. These PS+ platelets subsequently sort to the perimeter of the mass via platelet contraction. It remains unclear how thrombin and fibrin may alter PS+ platelet sorting within a clot. Here, we used an 8-channel microfluidic assay of clotting over collagen (± tissue factor) at 100 s-1 initial wall shear rate to investigate the roles of thrombin and fibrin in PS+ platelet sorting. Temporal PS+ platelet sorting was measured using a Pearson correlation coefficient between the annexin V distribution in a clot at 9 minutes versus 15 minutes. Spatial PS+ platelet sorting was measured using an autocorrelation metric of the final annexin V distribution. By 6 minutes, PS+ platelets were distributed throughout the platelet deposits and became highly spatially sorted by 15 minutes when thrombin and fibrin were blocked with PPACK. Fibrin polymerization (no PPACK) attenuated temporal and spatial PS sorting and clot contraction. With GPRP added to block fibrin polymerization, PS sorting was prominent as was clot contraction. Exogenously added tissue plasminogen activator drove fibrinolysis that in turn promoted clot contraction and PS sorting, albeit to a lesser degree than the PPACK or GPRP conditions. Clots lacking fibrin displayed 3.6-times greater contraction than clots with fibrin. PS sorting correlated with clot contraction, as previously reported. However, fibrin inversely correlated with both percent contraction and PS sorting. Fibrin attenuated clot contraction and PS sorting relative to clots without fibrin.
The de-thrombotic effect of N-acetylcysteine is induced by the interaction with von Willebrand Factor and the inhibition of platelets
Yiyuan (Daniel) Zhang, Scott L. Diamond
AbstractRecent arteriole thrombosis studies proposed a possible solution by administering N-acetylcysteine (NAC) to reduce the size of von Willebrand Factor (VWF) fiber to mitigate, cure or prevent arteriole thrombosis. NAC has been proven to be a promising drug for many diseases; however, although the antithrombic efficacy of NAC has been confirmed in various studies, the cause of its efficacy should not be concluded hastily to its ability to disintegrate VWF fiber, since experiment results also have shown that NAC cannot digest VWF that was already formed under pathological shear rate. Therefore, understanding the antithrombotic effect of NAC requires a more wholistic perspective that includes the interactions between platelet, VWF, and all other factors that attribute to thrombosis formation. Microfluidic experiments for in vitro simulation of arteriole thrombosis formation and the antithrombotic efficacy of NAC was conducted using 8-channel device with a shear inducing region in each flow chamber, vacuum-mounted to collagen/VWF surfaces forming 8 parallel-spaced prothrombotic patches. PPACK-treated blood was perfused across the 8 channels by withdrawal through a single outlet under pathological wall shear rate (5,100 s-1). Once a significant thrombosis is formed (~ 100 s), whole blood with 30mM NAC was switched in some channels to observe the antithrombotic effect of NAC under epifluorescence microscopy. Our results showed that NAC did induce a significant de-thrombotic effect, but it’s a cofactor of VWF interaction and platelet inhibition: it may have prevented aggregation of VWF, thus yielded smaller VWF fibers, and inhibited platelets thus prevented activation upon VWF.
Energy and Catalysis
Guiding Cobalt Oxide Nanoparticle Design for Energy Applications using DFT
Anthony Curto, Emma Glasser, Aleksandra Vojvodic
AbstractIn an effort to move towards a more sustainable future, improvements are needed for a wide range of materials design problems. Cobalt oxide is a valuable material that can is used in various energy applications, such as, a cathode in batteries or a catalyst. Density Functional Theory is a computational tool that can be used to study material structures and properties, helping to accelerate the material design process. Doping cobalt oxide nanoparticles with other metals has been shown to improve catalytic ability (by Fe-doping) and battery capacity (by Al-doping). By using a scheme utilzing DFT calculations of well-defined experimental systems, we are able to illustrate how nanostructuring materials design can improve material performance. Our detailed study on Fe-doped CoOx nanoislands for the Oxygen Evolution Reaction (OER) demonstrates the importance of site-specific catalyst design. Fe has anisotropic doping patterns in CoOx and the role of Fe is driven by where it is located in the system. Similarly, Al-doping of LiCoO2 increases long term battery capacity with the distribution of Al effecting this improvement. This work elucidates the reason behind these improvements and provides insight in how to further improve cobalt oxide materials for energy applications.
Miniature high energy density primary zinc air battery
Yanghang Huang, Qi Yang, Jingwen Zhang, Vihsal Venkatesh, Sue Ann Bidstrup Allen, Mark Allen
AbstractThis study focuses on the development of a miniature, high energy density zinc air battery (ZAB) for powering microrobotic systems. One design constraint associated with this miniature battery is the limited volume available for the electrolyte, which impacts the availability of mobile hydroxide ions. Therefore, it is crucial to understand the net consumption of mobile species and design a miniature ZAB that incorporates the electrolyte limitation. The mechanisms of two side effects including carbonation and slow zincate decomposition are studied, and the consumption rates are measured through titration with a Barium- Ethylenediaminetetraacetic acid (Ba-EDTA) additive. A miniature ZAB configuration is demonstrated with a volumetric energy density of 1575 Wh/L and gravimetric energy density of 402 Wh/kg.
Magnesium Oxide Looping for Direct Removal of CO2 from the Atmosphere
Noah McQueen, Peter Kelemen, Greg Dipple, Phil Renforth, Jennifer Wilcox
AbstractTo avoid dangerous climate change, new technologies must remove billions of tonnes of CO2 from the atmosphere every year by mid-century. Here we detail a land-based enhanced weathering cycle utilizing magnesite (MgCO3) feedstock to repeatedly capture CO2 from the atmosphere. In this process, MgCO3 is calcined, producing caustic magnesia (MgO) and high-purity CO2. This MgO is spread over land to carbonate for a year by reacting with atmospheric CO2. The carbonate minerals are then recollected and re-calcined. The reproduced MgO is spread over land to carbonate again.
In the proposed process, multiple carbonation plots are used in parallel and recalcined at different times throughout the year. The number of carbonation plots is optimized to keep the calciner continuously operational based on the calcination time, a loading factor, and a capacity factor of 90% for the central calcination facility. By varying the maturation time of the carbonation plots, many plots can correspond to one central calcination facility. This allows for the process to continuously utilize process equipment, as well as increases the scale of operation without incurring additional capital costs.
We show this process could cost approximately $46–159 tCO2−1 net removed from the atmosphere, considering grid and solar electricity without post-processing costs. This technology may achieve lower costs than projections for more extensively engineered direct air capture methods. Further verification targets the ability for repeated cycling via accelerated carbonation-calcination experiments to determine the cyclic uptake of CO2 and the lifetime of the magnesium feedstock.
Enhancing the Activity of Perovskite Anodes with low metal loadings via ALD
Julian M. Paige, Raymond J. Gorte, John M. Vohs
AbstractPerovskite (ABO3) fuel electrodes for solid oxide electrochemical cells (SOECs) have been demonstrated to be promising alternatives to traditional Ni-cermet anodes. Their redox stability and enhanced sulfur & coking tolerance compared to Ni-cermets makes them attractive candidates for operating under complex conditions. However, they lack sufficient catalytic activity and thus require the addition of catalysts through nanoparticle infiltration, or metal exsolution from the host perovskite. While infiltrated catalysts degrade overtime from sintering and coking, exsolved catalysts typically do not. Both methods however require high loadings of metal to achieve sufficient activity due to low dispersions. Atomic layer deposition (ALD) is a technique that allows one to tune the chemical composition of a surface by adding sub-monolayer amounts of material. Metals and metal-oxides deposited by ALD often have unique properties, high stability, and high dispersions which are attractive for catalysis. In the present study SOECs with LaxSr1-xCryMn1-yO3-YSZ composite electrodes were fabricated and various catalysts were incorporated into the electrode either by infiltration, exsolution, or ALD. The performance of the resulting SOECs were characterized by Electrochemical Impedance Spectroscopy & I-V Polarization curves.
Cation transport through ionic layers in sulfonated crystalline telechelic polyethylenes
Benjamin A. Paren, Manuel Häußler, Stefan Mecking, Karen I. Winey
AbstractWe present a set of sulfonated telechelic polyethylene ionomers that demonstrate ion transport of metal cations within layered ionic aggregates in a crystalline polymer matrix. These precise ionomers consist of 48 backbone carbons with sulfonated end groups that are fully neutralized by a counterion, C48(SO3X)2 (X=Li+ or Na+). The morphology is characterized using X-ray scattering, and these telechelic polyethylenes exhibit well defined ionic layers and a variety of crystalline backbone morphologies below the melting point, Tm. The temperature-dependent ionic conductivity is characterized using electrical impedance spectroscopy. The polyethylene backbone packs in a hexagonal crystal at high temperatures in both the Li+ and Na+– containing systems, with an Arrhenius activation energy (Ea) for ion transport of 120 and 53 kJ/mol, respectively, indicating decoupled ion transport through the layers. The Ea in the hexagonal regime is significantly lower than Ea in the room temperature backbone morphologies of these polymers, orthorhombic in C48(SO3Na)2, and disordered crystals in C48(SO3Li)2. The low Ea for ion transport, 53 kJ/mol, in the hexagonal regime of C48(SO3Na)2 is a promising sign for the ability of ionic layers to facilitate ion transport in crystalline polymers, for potential application as solid polymer electrolytes.
Innovation Pathways to Decarbonize Kiln and Furnace Technology
Maxwell Pisciotta, Hélène Pilorgé, Justine Davids, Daniel Maynard, Zachary Sasso, Jennifer Wilcox
AbstractThe industrial sector makes up approximately 22% of U.S. carbon dioxide (CO2) emissions, of which cement, lime, glass, and iron and steel production contribute roughly one third. This work identifies pathways to decarbonize incumbent kiln and furnace technology used to produce these industrial materials.
Producing cement, lime, glass, and iron and steel requires large-scale heating in a kiln or furnace. Oftentimes, this heating is achieved through the burning of fossil fuels that release harmful CO2, among other greenhouse gases into the atmosphere. Cement and lime are produced by the use of a rotary kiln, which heats calcium carbonate (CaCO3) to approximately 1300°C, releasing CO2 and resulting lime (CaO) product. For glass production, natural gas-fired hearth kilns are used to melt primarily silica sand (SiO2) mixtures at temperatures around 1500°C to create a molten mixture that is easily shaped. Iron and steel can be produced through the use of a direct reduced iron with electric arc furnace (DRI/EAF) process or blast furnace and basic oxygen furnace (BF/BOF) process. The DRI/EAF process is more often used in the recycling of steel, whereas the BF/BOF process is more often used in primary steelmaking. The EAF can reach temperatures around 1750°C during the steel recycling process and is powered by electricity. The CO2 emissions related to the EAF are from the steel refining and the indirect emissions from the electricity use. The BF/BOF process uses internal natural-gas combustion at temperatures around 2150°C. Within this process, the CO2 emissions both come from the iron reduction and refining processes as well as from the combustion of natural gas.
The CO2 released directly from the process of manufacturing these materials is classified as process emissions as it comes directly from the raw material. When fossil fuels are used to heat the kilns or furnaces, the CO2 that results from their burn are classified as stationary combustion emissions. CO2 capture and storage (CCS), oxy-combustion, indirect heating, fuel switching, and other innovative pathways have been identified to either reduce or capture the CO2, while still meeting the market demand.
By analyzing each of the innovative pathways, their current readiness for deployment, and the constraints they pose for each process, further research plans can be developed that incorporate incumbent economic drivers, as well as modifications and advancements required to adopt innovative solutions to reduce industrial CO2 emissions. Paired with the locations and lifetimes for each existing kiln or furnace in current use, strategic plans for adoption of updated technology can be realized. These strategies range from the colocation of electric kilns with low-/no-carbon electricity sources to fuel-switching in areas where biomass is readily available.
Soft Matter
A Gallery of Trajectories for Motile Bacteria at Fluid Interfaces
Jiayi Deng, Mehdi Molaei, Nicholas Chisholm, Kathleen J. Stebe
AbstractActive colloids can accumulate at fluid interfaces and move in manners strongly influenced by this complex 2D fluid environment. We seek to understand their motions and their consequences to develop building blocks for 2D materials that are truly surface active. Bacteria are important examples of active or self-propelled colloids. Because of their directed motion, they can become trapped and swim adjacent to the interface via hydrodynamic interactions, or they can adsorb directly and swim in an adhered state. We study Pseudomonas aeruginosa PAO1 on or near hexadecane-water interfaces as a model system. In addition to characterizing the ensemble behavior of the bacteria, we have observed a gallery of distinct trajectories of individual swimmers on and near fluid interfaces. These include Brownian diffusive paths, curvilinear trajectories including curly paths with radii of curvatures larger than the cell body length and rapid pirouette motions with radii of curvature comparable to the cell body length. Finally, we see interfacial visitors that come and go from the interfacial plane. We characterize these individual swimmer motions and propose the relevant implications on microrobots and interfacial transportation.
Surface Segregation and Wetting of Grafted Nanoparticles in Polymer Nanocomposite Films
Shawn Maguire, Michael J. Boyle, Connor R. Bilchak, John Derek Demaree, Nadia M. Krook, Andreea-Marie Pana, Austin Keller, Patrice Rannou, Manuel Maréchal, Kohji Ohno, Russell J. Composto
AbstractThe segregation and wetting of polymer grafted nanoparticles (NP) to the free surface of a polymer nanocomposite film is driven by both surface energy and thermodynamic forces. Here, we probe these two contributions in a model system of PMMA grafted silica NPs in a poly(styrene-ran-acrylonitrile) (SAN) matrix using grazing-incidence Rutherford backscattering spectrometry (GI-RBS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) as a function of thermal annealing temperature and time. Studies are performed above the lower critical solution temperature (LCST) of this system to track the morphological evolution during phase separation and wetting. With increasing annealing time at shallow quench depths above the critical point, a monotonic increase in PMMA-NP surface excess is observed. Upon annealing at deeper quench depths, we monitor a further increase in surface coverage of nanoparticles, attributed to a stronger thermodynamic driving force for phase separation, namely the Flory-Huggins interaction parameter between the PMMA grafts and SAN matrix. Using the measured surface excess values of PMMA-NPs at multiple annealing times and temperatures, the apparent diffusion coefficients of the grafted nanoparticles are extracted and compared to theoretical predictions. These studies demonstrate the ability to control nanocomposite surface morphologies, which have attractive technological applications where surface dependent properties such as wettability, durability, and the friction are important.
Assembly of Polyelectrolyte-Nanoparticle Membranes at Water-water interfaces
Wilfredo Mendez, Kathleen Stebe, Daeyeon Lee
AbstractWe study the formation of structures at water-water interfaces. Assembly at water-water interfaces differs significantly from the more typical setting of interfaces between immiscible fluids of differing polarity. On these more typical interfaces, molecules and particles readily assemble to reduce the high interfacial tensions or surface energies that are absent in our system. Water-water interfaces are particularly powerful scaffolds owing to the mild solution conditions and the fact that the interface is in contact with the two adjacent water phases. Such an open scaffold is able to accept material from both bulk phases. We have fabricated membrane-like structures at these interfaces with interesting structures and transport properties. We study assembly of polyelectrolytes (PEs) and nanoparticles (NPs) at an interface between two aqueous phases formed from polyethylene glycol (PEG) and dextran. Motivated by the analogies and differences between our system and layer-by-layer (LbL) assembly of NPs and PEs, we explore the importance of osmotic stress imbalances, flux of species and the presence of salts in regulating the membrane structure and rate of growth to gain mechanistic insight into structure formation.
Effect of Extreme Nanoconfinement on the Thermodynamics of Multiphasic
Anastasia Neuman, Daeyeon Lee, Robert Riggleman
AbstractPolymer infiltrated nanoparticle films (PINFs) have greatly improved macroscopic properties over polymers alone, or even polymers with macro or micro-scale fillers. Due to their unique properties, PINFs have proven useful in numerous practical applications such as gas separation or reverse osmosis membranes that allow for both high selectivity and high gas permeability, as well as for packaging with specific barrier property requirements. Capillary rise infiltration (CaRI) and solvent-driven infiltration of polymer (SIP) have emerged as powerful methods to prepare PINFs with a wide range of polymers and nanoparticles. My work focuses on understanding the thermodynamics of PINFs with two different polymers. We hypothesize that thermodynamics and resulting morphology will be significantly affected by extreme nanoconfinement in PINFs. Additionally, changing interactions between the two polymers and particles will greatly impact the phase behavior of polymer blends. We expect to see wetting transitions which induce local phase separations near interfaces at thermodynamic conditions where mixing is stable in the bulk. Overall we expect to deduce insight about the miscibility and phase behavior of polymer mixtures under confinement in nanoparticle packings to inform the design of future PINFs.
Enzyme-powered surface-adherent protocells from double emulsion-templated polymersomes
Jessica O’Callaghan, Daeyeon Lee, and Daniel A. Hammer
AbstractProtocells are synthetic cells that mimic the size and organization of biological cells but can be built from novel components. Protocells membranes can be made from a variety of surfactants ranging from phospholipids (liposomes) to diblock copolymers (polymersomes). Unlike liposomes, which are fragile and have limited chemical functionality, polymersomes can be imparted with advanced responsiveness and unique properties that widen the palette of functionalities that can be incorporated within the protocell membrane.
A goal of our research is to make motile protocells whose motion is driven by enzymatic reactions. Many synthetic motile systems rely on asymmetry for propulsion in bulk solution. In this case, we drive the motion of adherent asymmetric particles using enzymatic reactions. The motive for using enzyme catalysis to drive particle motion is based on the demonstrated principle that enzymatic turnover of substrate to product generates a displacement force. Our prior work demonstrated that catalase-containing surface-adherent protocells made from poly(ethylene oxide) – b – poly(1,2 butadiene) display random autonomous motion in the presence of hydrogen peroxide. However, these experiments used heterogenous populations of protocells made from thin-film rehydration. To develop a more elegant platform for enzyme-driven motility, uniform microcapsules are templated from water-in-oil-in-water (W/O/W) double emulsions droplets, allowing for precise control over the size of the capsules as well as their interior and membrane composition. Previous work on microfluidic templating relied on slow evaporation of the middle organic phase consisting of a highly volatile good solvent (chloroform) and a less volatile poor solvent (hexane) to form an intact bilayer with a small patch of excess polymer. Because this process could take two weeks, processing severely limited the biomedical applications of double-emulsion templated protocells. In this study, we use a surfactant-assisted strategy to induce complete dewetting of polymersomes from the double emulsion droplets to form polymersomes with uniform membrane thickness within minutes. In particular, droplet collection into a solution containing PVA adjusts the interfacial energies in the W/O/W emulsion system and ensures complete separation of the inner aqueous droplet from the oil shell. Complete dewetting is seen within 10 minutes following double emulsion fabrication at sufficiently high concentrations of PVA. We demonstrate the use of these capsules by incorporating coacervating proteins within the lumen to self-assemble into membraneless organelles, as one step toward the larger goal of recreating a natural cell using designer bio-inspired materials. Moreover, we attach enzymes to the shell of these capsules and examine their motion both in solution and on adherent surfaces in response to enzymatic turnover, using catalase, urease, and other enzymes.
Nanoscale Morphologies and Ionic Conductivities of Precisely Segmented Polyethylene Sodium-Sulfonates
Jinseok Park, Anne Staiger, Stefan Mecking, Karen Winey
AbstractWe investigated the polyethylene-based single-ion conductors containing periodically placed sodium sulfonates with the varying length of ethylene segments (PESxNa, x = 10, 12, 18). At 25°C, all polymers are semicrystalline with the layered ionic aggregates of which the ordering is higher with the longer ethylene units. For PES12Na and PES18Na, the transition of ionic layers into the Ia3d gyroid morphology was observed by the in-situ X-ray scattering experiments upon the melting of polyethylene segments, and further transition of gyroid to hexagonal morphologies with increasing temperatures. On the other hand, PES10Na exhibited a layered to the hexagonal transition of ionic aggregates above the melting temperature without the transition into gyroid morphologies. These order-to-order transitions were described by the phase diagram of the inverse temperature vs volume fraction of polar segments and this phase diagram resembled the conventional block copolymer phase diagram. Na+ conductivities indicate that the gyroidal ionic aggregates exhibit higher ionic conductivities than the hexagonally packed ionic aggregates. The conductivity gap between the gyroidal and hexagonal morphologies is dependent on the characteristic lengths of nanoscale ionic aggregate morphologies. This study further provides the design rules to improve the ionic conductivities of periodic polyethylene sulfonates as single-ion conductors.
Polymer-infiltrated Nanoplatelets Films via Flow Coating and Capillary Rise Infiltration (CaRI)
Yiwei Qiang, Kevin T. Turner, Daeyeon Lee
AbstractAlignment of highly anisotropic nanomaterials in a matrix of polymer yields nanocomposites with unique mechanical and transport properties. Conventional methods of nanocomposite film fabrication, however, tend to be time-consuming and laborious and also are not ideal for manufacturing composites with very high concentrations of anisotropic nanomaterials, potentially limiting the widespread implementation of these useful nanocomposite structures. In this work, we present a scalable approach to fabricate polymer-infiltrated nanoplatelet films (PINFs) based on flow coating and capillary rise infiltration (CaRI) and study the processing-structure-property relationship of these PINFs. We show that films with gibbsite (Al(OH)3) nanoplatelets (NPTs) aligned parallel to the substrate can be prepared using a simple flow coating process. NPTs are highly aligned with a Herman’s order parameter of 0.96 with a high packing fraction > 80 vol%. Such packings show significantly higher fracture toughness compared to spherical nanoparticle (NP) packings. By depositing NPTs on a polymer film and subsequently annealing the bilayer above the glass transition temperature of the polymer, polymer can infiltrate into the tortuous NPT packings though capillarity. We observe larger enhancement in the modulus, hardness and scratch resistance of NPT films upon polymer infiltration compared to spherical NP packings. The excellent mechanical properties of such films benefit from both thermally promoted oxide bridge formation between NPTs as well as polymer infiltration increasing the strength of NPT contacts. We believe our approach is widely applicable to highly anisotropic nanoparticles and allows the generation of mechanically robust PINFs for multiple applications.
Controlling the Emulsion Type Using Adjustable Polyelectrolyte-Surfactant Complexes
Joseph Rosenfeld, Daeyeon Lee
AbstractThe combination of polyelectrolytes and ionic surfactants in precise proportions presents the possibility of producing a new class of emulsifiers with tunable emulsification properties. We use chitosan, a naturally sourced cationic polyelectrolyte along with anionic surfactant dioctyl sulfosuccinate sodium, also known as aerosol-OT (AOT), to demonstrate that different emulsion types can be stabilized, and phase inversion emulsification (PIE) can be induced in situ via changes in the water-phase pH and the molar ratio of the surfactant to the repeat unit of the polyelectrolyte. Confocal microscopy of the emulsions shows that the morphology can be changed from O/W to O/W/O to W/O by varying the surfactant to polyelectrolyte molar ratio at a fixed aqueous-phase pH while maintaining droplet sizes in the range of micrometers to tens of micrometers. Measurements of the oil (toluene)−water partition coefficient suggest that controlling the emulsion type relies on the ability of the surfactants to partition from the bulk oil to the bulk water phase and to induce polyelectrolyte−surfactant aggregation. We confirm this hypothesis using different combinations of polyelectrolytes and surfactants with different partitioning behavior. Changes in the water-phase pH in situ induce phase inversion only between particular states, which suggests that the complexes at the interface are in a kinetically trapped state and are not equilibrium structures.
Contactless, Reversible Droplet Contact Angle Modulation by Space Charge Injection
Joe (Paradorn) Rummaneethorn, Daeyeon Lee
AbstractHere we demonstrate a contactless, reversible method for droplet contact modulation on chemically inert substrates using corona discharge-based space charge injection technology. This method enables droplet contact angle modulation via an external physical stimulus—rather than altering surface chemistry—without direct droplet contact, which may not be desirable due to closed microfluidic device settings or potential damage to enclosed biological materials. Without prior surface patterning, there is more flexibility in droplet positioning, and the charger injector probe provides spatiotemporal control on droplet contact angle modulation. This technology may be applied for deposition of droplet-enclosed materials through wetting state modulation, after which the materials may be analyzed by techniques such as mass spectrometry. The current study shows that reversible wetting is achievable even in nonconducting continuous phases. The reverse step, here dewetting, can be achieved by two different ways: (1) applying an oppositely charged corona, or (2) removing the voltage and allowing system to discharge. While the voltage requirement depends on the dielectric strength of the medium in contact with the probe, the system becomes more complicated if the probe and droplet are exposed to different media, which is often the case and also of interest for generality. Modeling the system as a multi-dielectric capacitor, we seek to theoretically solve for the voltage distribution in each dielectric layer to assess the necessity of inducing dielectric breakdown in every layer between the probe and droplet for the charge injection to effectively occur.
Exploring Core-shell Bottlebrush Copolymer Architecture’s Effect on the Block Copolymer Phase Diagram
Christian Tabedzki, Robert A. Riggleman
AbstractBottlebrush copolymers (BBCPs), an architecture where chains are grafted off a neutral backbone, offer several advantages that make BBCPs easier for processing, namely fast ordering kinetics, large domain sizes, and long-range order. Core-shell bottlebrush polymers, where the grafts are linear diblock chains, are a potential alternative to linear diblock copolymers. Using a combination of analytical Random Phase Approximation (RPA) and theoretically informed Langevin dynamics (TILD) simulations, we compare the order-to-disorder transition points (ODTs) of our novel architecture against the linear BCPs. We show that increasing the graft length and the backbone length decreases the required chemical dissimilarity χN needed to achieve an ordered state. The constrained nature of the inner monomers yields an entropy penalty, shifting the critical composition to lower volume fractions. Backbone contraction through the transition points as a function of graft length and composition was also explored.
Soft glassy dynamics and rheology: A damped soft-sphere model
Amruthesh Thirumalaiswamy, Robert A Riggleman, John C Crocker
AbstractThe mechanical response of a diverse family of seemingly disparate materials, like foams, cells, and emulsions, exhibiting a similar response to applied deformation, has largely defied explanation. One example being their rheology, where the complex modulus shows a weak power-law dependence on frequency, that we recently postulated could be a direct manifestation of the fractal energy landscape of these materials. In this work, we extend our previous study by per-forming bubble dynamics simulations with damped, non-inertial bubbles evolving similar to ripening observed in foams. We study the coarsening system in the dynamic scaling state, and the resulting physical and dynamic properties over a range of damping effects. As shown before, the under-damped system gives rise to spatially correlated dynamics with avalanches while traversing fractal paths in 3N-dimensional configuration space through super-diffusive motion. Further, we investigate the statistical nature of avalanches in time and their disappearance in the over-damped limit, and the corresponding changes in the rheology of the system. Lastly, we study the aging of the system after strong perturbations and look for signatures of self-organization in the dynamical steady state.
Bicontinuous biphasic emulsion gels for catalysis and separation applications
Giuseppe Di Vitantonio, Tiancheng Wang, Daeyeon Lee, Kathleen J. Stebe
AbstractSimultaneous operation of catalyzed reaction and separation had transformative impact increasing the efficiency of chemical processes; very successful particle-stabilized emulsion-based phase-transfer catalysis has been developed, however the traditional water in oil/oil in water emulsion cannot perform a steady and robust separation of the product. A bicontinuous particle-stabilized emulsion (bijel) can overcome these limitations, in our lab we developed the solvent-transfer induced phase separation (STRIPS) technique to produce such material in a simple, flexible and continuous fashion.
We show how bijel chemistry can be tuned to improve its mechanical and chemical properties, as well as introducing catalytic nanoparticles in the bijel scaffold.
We use this soft material to run simultaneous reaction and separation taking advantage of the different water affinity of reagent and products.
We are able to perform a broad variety of chemical reactions in bijels: non catalytic, homogenous catalysis and heterogenous catalysis, accessing temperature ranges of about 100°C.
Patterned Nanocomposite Films via Leaching-enabled Capillary Rise Infiltration (LeCaRI)
R. Bharath Venkatesh, Syung Hun Han, Daeyeon Lee
AbstractPolymer infiltration into the voids of nanoparticle assemblies has become a unique way to make polymer nanocomposites which show remarkable enhancement in mechanical and heat transfer properties due to a high loading of nanoparticles and large interfacial contact between the nanoparticle and the polymer. Previously, solvent based and thermal routes have been used to induce motion of polymer from a glassy film into the nanoparticle packing. Leaching-enabled capillary rise infiltration (LeCaRI) is a powerful method to generate composites by inducing leaching of uncross-linked chains from an elastomer network into the pores of a nanoparticle packing at room temperature. A unique feature of this method is the ability to create both self-erasing and permanently patterned microdomains of composites. Laterally graded patterns and features can be fabricated to produce surface structures with laterally graded optical, mechanical and wetting properties which otherwise require intense preparation processes. LeCaRI can be made universal in its applicability by depleting an elastomer of the uncrosslinked chains, loading it with a new polymer, and inducing infiltration. New results on the thermodynamics of loading of polymers with low glass transition temperature into depleted gels will be presented.
Effect of nanopore geometry in the conformation and vibrational dynamics of a highly-confined molecular glass
Haonan Wang, Kenneth Kearns, Zahra Fakhraai
AbstractThe effect of nanoporous confinement on the glass transition temperatures (Tg) are poorly understood, and strongly depend on the specific system. Here we study the molecular origins of this effect in molecular glass, N,N’-Bis(3-methylphenyl)-N,N’-
Scalable Manufacturing of Hierarchical Biphasic Bicontinuous Structures via Vaporization Induced Phase Separation (VIPS)
Tiancheng Wang, Giuseppe Di Vitantonio, Kathleen J. Stebe, and Daeyeon Lee
AbstractStudies of bicontinuous interfacially jammed emulsion gels (bijels) have greatly expanded the possibilities of multiphasic systems. We have previously introduced the solvent transfer induced phase separation (STRIPS) method to prepare bijels from ternary mixtures of oil, water and co-solvent (ethanol). Although STRIPS enables continuous processing, the requirement of the outer aqueous phase limits their applications to liquid environments. Enabling production of bijels in air would further expand their applications in areas such as coatings and surface modification applications. In this work, we demonstrate a new method of producing three dimentional multiphasic structure (including bijel) via vapor-induced phase separation (VIPs). In VIPS, the evaporation of the co-solvent, from a ternary mixture of oil, water and ethanol, induces phase separation. Particles present in the mixture attaches to the interface and arrests the phase separation between water and oil. VIPs enables the fabrication of films and coatings via spreading or spraying particle-laden suspension onto a surface without the need for an outer aqueous phase. The structure of VIPs films on different substrates are characterized, and the influence of initial composition and quenching depth are investigated.
Large-scale On-chip Manufacturing of Granular Hydrogels
Alex (Jingyu) Wu, Sagar Yadavali, David Issadore, Daeyeon Lee
AbstractMicron-sized hydrogel particles (Microgels) with different morphologies have attracted many attentions in drug delivery and tissue engineering. One method to produce particles with different morphologies is to incorporate the use of UV light source with droplet microfluidics. However, the throughput of single-channel microfluidic generation is typically limited to less than 200ug/hr, making it not feasible for researches that require large sample volume or industrial-scale manufacturing. While the throughput of the microgel generation can be increased by scaling out of the droplet generators, channel clogging by on-chip solidified particles becomes a significant challenge. Unlike liquid and bubble droplets, solidified particles have limited deformability and tend to aggregate due to colloidal forces. Clogged channels will block the passage of subsequent particles and greatly disturb the pressure drop of the flow, inducing a chain clogging events. This will thus stop the continuous manufacturing and make devices non-reusable.
My research focus on developing a highly parallelized microfluidic platform for large-scale microgel synthesis. We adopt a “free-fall” design strategy to overcome the aforementioned clogging challenge, utilizing the laser micromachining capability to pattern and drill large opening channels on the back side of the device. A three-dimensional microfluidic platform is developed and a model photopolymerizable gel, PEGDA, is used, showing the possibility of manufacturing anisometric microgel particles in kilogram scale.
The roles of blending and thickness on determining the mechanical properties of free standing ultrathin films
Tianren Zhang, Robert Riggleman
AbstractAlthough many studies have analyzed the various properties of glassy polymer thin films, the failure mode and nonlinear mechanical response has only recently received attention. Due to competing effects between reductions in the entanglement density and increased mobility near the free surfaces, it is not clear whether one should anticipate embrittlement or improved ductility. In this study, we constructed binary blend polymer thin films by incorporating the short chains as diluents into the highly entangled polymer systems with different compositions across several film thickness. Due to the presence of a large portion of the high mobility particles near the free surface, the films of thickness below 10 are much less ductile than the films of thickness larger than 20 for both blend and homopolymer thin films, despite the insensitivity of entanglement density to the thickness of the polymer thin films. The dependence of mechanical properties on the thickness is weak when the film is larger than 20, especially for highly entangled system N=250 in the homopolymer thin films. With diluent polymers added, the films become less ductile than the homopolymer with purely highly entangled polymer chains, and the mechanical properties of the polymer thin films are affected most when the added diluents are unentangled polymers. Under the same blend composition, the mechanical stability of the films with unentangled diluents are much weaker compared to the ones with slightly entangled diluents. Further, we noticed that there is a competing effect between free surface and entanglement network , where the free surface interaction dominates the mechanical behavior when the thickness of the polymer film is less than 10 and entanglement network plays more important role when the thickness is larger than 20σ.