Squishy Materials Seminars (SMS)
What is SMS?
UVA has an increasing community of researchers whose work deals with soft/squishy materials - liquids, polymers, foams, gels, colloids, granular materials, as well as most soft biological materials. This is an opportunity for us all to come together. Nothing formal: simply a venue to meet other people with mutual interests over cookies and coffee, and talk about research or anything else. Squishy audience members typically include physicists, chemists, engineers, and biologists. The audience is strongly encouraged to ask questions anytime during the seminar. We have two kinds of sessions:
Long Talks: This session typically features talks from local faculty members and outside speakers to who happen to visit C’ville. Postdocs and graduate students are also welcome! In each session, we will have one talk of ~45 minutes long.
Short Talks: This session features talks from students and/or postdocs. In each session, we will have 2-3 short talks, and each talk is of 15-20 minutes long.
When is SMS?
Every Wednesday 3:00 – 4:15 pm.
Where is SMS?
Wilsdorf 200.
Who can attend SMS?
Anyone interested in squishy materials: Undergraduates, graduate students, postdocs, researchers, and faculty.
How can I find out about future SMS meetings?
Subscribe to Squishy Materials mailing list.
Interested in giving a talk?
Please send an email Prof. Liheng Cai or Prof. David Green.
We are greatful to the finanical support from Dean's Office of UVA Engineering!
Current Schedule
November 6, 2019
Speaker: Holly M. Mayton(Berger Group), Nicholas Cornell (Griffin Group)
Title: Reducing bacterial biofilms with an engineered enzyme (Holly M. Mayton)
Abstract: Biofilm formation is a major cause of microbial persistence on food surfaces, medical devices, and dental implants because the biofilm matrix has been shown to provide pathogens and other bacteria with protection from common disinfection approaches. The potential of an enzyme-based biocide has been investigated as a supplement to common disinfection practices for preventing bacterial adhesion and removing mature biofilms. Crystal violet staining of biofilms formed in multi-well polystyrene plates has been used to demonstrate the efficacy of enzymatic biofilm prevention and removal on E. coli O157:H7, E. coli 25922, Salmonella Typhimurium, and Listeria monocytogenes. In the presence of 0.1 mg/mL enzyme, biofilm development was significantly inhibited for all bacteria, with a maximum of 41 ± 7% reduction for E. coli O157:H7. Effectiveness of mature biofilm removal varied by bacteria species type, with a maximum of 35 ± 12% reduction for E. coli O157:H7. A microfluidic flow cell was used to directly observe and quantify the impact of enzyme rinses on E. coli O157:H7 cells adhered to spinach leaf surfaces. In the flow cell, enzyme rinses resulted in significantly greater cell removal than water, representing a reversal of initial phases of biofilm formation. The homology of the enzyme employed in this work is similar to that of other glycosyl hydrolases; therefore, it is hypothesized that the enzyme plays a role in the direct degradation of extracellular polymers. Electron microscopy of treated and untreated cells reveal major modification to surface polysaccharide structures. Additionally, changes in cell surface hydrophobicity were measured using the microbial adhesion to hydrocarbons (MATH) test and provide further evidence of changes to the cell surface. These results present a strong case for further development and optimization of enzyme activity to be applied as an organic additive for minimizing food safety risks and clinical infections associated with biofilms.
Title: Variable Immobilization of Glycosaminoglycans for Controlled Biomaterial-Protein Interaction (Nicholas Cornell)
Abstract: Glycosaminoglycans (GAGs), such as chondroitin sulfate (CS) and heparin, are naturally occurring linear polysaccharides that regulate both homeostasis and wound healing. Specifically, GAGs are found throughout the extracellular matrix and interact with soluble proteins (e.g. growth factors) through electrostatic interactions with downstream regulation of cell signaling and behavior. The strength of these interactions is heavily influenced by the structural flexibility of the GAG to conform to proteins. Diabetic wounds, a particularly challenging class of skin wound, present numerous hurdles to effective tissue regeneration, including both pathologically low levels of GAGs. Previously, GAGs have been incorporated into wound healing biomaterials as highly modified polymeric backbones, however we hypothesize that this manner of incorporation greatly reduces their conformational freedom and, subsequently, their bioactivity. Our lab is interested in immobilizing GAGs within our biomaterial platform in a manner which more closely resembles the body’s natural linear presentation. We have developed two distinct forms of GAGs which can be easily incorporated within our Microporous Annealed Particle (MAP) platform technology. Our biomolecular investigations have revealed that the extent of GAG modification affects both the strength of protein-GAG and protein-biomaterial interactions.
November 20, 2019
Speaker: Prof. Sergei A. Egorov, Department of Chemistry
Title: Isotropic-Nematic Behavior of Semiflexible Polymers in the Bulk and under Confinement
Abstract: Density functional theory will be presented that is suitable for studying the isotropic-nematic phase transition of semiflexible polymers both in the bulk and under planar confinement. The effects of the density and temperature, as well as chain length and chain stiffness on the bulk phase diagram will be analyzed. The phenomenon of capillary nematization in a slit geometry will be discussed. The predictions of Density Functional Theory will be compared with previous theories and with extensive Molecular Dynamics simulations.
December 4, 2019
Speaker: Prof. Ku-Lung (Ken) Hsu, Department of Chemistry
Title: Chemical Biology and Chemistry for Translational Lipid Biology and Beyond
Abstract: Lipids represent a rich model system for understanding how nature maintains cellular architecture (membrane building blocks), bioenergetics (energy stores), and communication (secondary messengers) through fine adjustments in enzyme metabolism. Embedded within lipid structures is chemical information that define their metabolic fate and function. Elucidating structure-function relationships of lipids in biological systems has been traditionally challenging because of the massive structural diversity of lipids in nature and lack of tools to selectively probe their function in vivo. I will describe efforts from my group to use chemical biology and mass spectrometry to gain fundamental insights into diacylglycerol (DAG) biology and the translational potential of modulating DAG pathways in inflammation and immuno-oncology.
Past Events
September 19, 2018
Speaker: Erica Hui (Caliari Group), James Tang (Lampe Group), Steven Merz (Green Group)
Title: Dynamically phototunable hydrogels to study cell mechanobiology (Erica Hui)
Abstract: While hydrogels are useful models for studying cell behaviors, most existing in vitro systems behave like elastic solids that fail to mimic native viscoelastic tissues and do not display time-dependent mechanics relevant in processes such as fibrosis. Here, we developed hydrogels via light-mediated thiol-ene addition reactions to allow for spatiotemporal control over crosslinking density. Covalent and supramolecular interactions were modulated to introduce viscoelasticity into the system, and photopatterning mimicked heterogeneous mechanical properties inherent in native tissue. We then used these substrates to interrogate hepatic stellate cell (HSC) mechanobiology in a model of myofibroblast activation. Compared to the elastic substrates, the viscoelastic hydrogels displayed higher loss moduli, frequency-dependent behavior, and showed stress relaxation. HSCs on soft viscoelastic gels showed decreased spread area and a more rounded morphology, but overall nuclear localization of myocardin-related transcription factor A (MRTF-A), a transcriptional co-activator that facilitates α-smooth muscle actin (α-SMA) expression, was shown to be independent of viscoelasticity. On patterned substrates, cells were found to preferentially spread and proliferate on stiffer regions, and feature size was shown to affect cell spread area. Overall, the hydrogels developed here will provide insight towards investigating the role that matrix mechanical properties play in regulating cellular processes involved in disease processes.
Title: Multicomponent and supramolecular self-assemblies as functional biomaterials (James Tang)
Abstract: Regenerative medicine aims to develop bioactive matrices that promote cellular interactions and elicit desirable regenerative behavior in vivo. This is particularly important in the context of ischemic stroke where a focal lesion forms forestalling the regrowth of brain tissue. Peptide-based molecules are used as building blocks to create supramolecular structures that emulate the properties of the native healthy extracellular matrix (ECM) within the central nervous system (CNS). In order to facilitate the regeneration of lost and/or damaged tissue, we propose using peptidic biomaterials that have the ability to emulate the properties of the native healthy extracellular matrix (ECM) within the CNS. We look to develop a combinatorial strategy involving computational modeling and experimental approaches to design and synthesize a family of novel multicomponent, self-assembling pentapeptide hydrogel (SAPPH) systems that mimic many of the biochemical and mechanical properties, such as porosity, pore size, viscoelastic properties, etc. found in the ECM. In addition, we will leverage the power of atomistic molecular dynamics simulations to examine the dynamical effects of systematically perturbing the pentapeptide sequence motif. This enables us to screen for a myriad of design candidates in silico, and promising leads that exhibit higher order self-assembling behavior will later be experimentally produced.
Title: Design and Characterization of Ultrasmall Monolayer Protected Nanoparticles (Steven Merz)
Abstract: Monolayer protected nanoparticles (MNPs) have a wide variety of applications from catalysis and photonics to biosensing and drug delivery. However, characterization of ultrasmall MNPs (<10nm) has proven difficult with traditional experimental techniques making the synthesis and design of these ultrasmall MNPs challenging. Our work looks to develop simple and robust characterization methods using both experimental and computational techniques. Experimentally we use Transmission Electron Microscopy (TEM) to assess nanoparticle shape and size and Matrix-Assisted Laser Desorption and Ionization (MALDI) to assess the degree of order present in nanoparticle monolayers. In addition, we model the systems using both Self-Consistent Field Theory (SCFT) and atomistic simulations to model these nanoparticle monolayers. We are then able to calculate predicted MALDI spectrum from these simulations which allows us to directly compare theory and experiment.
Inaugural Squishy Materials Seminar on September 19, 2018
September 26, 2018
Speaker: Prof. Baoxing Xu, Department of Mechanical and Aerospace Engineering
Title: Soft-Hard Material Integrations: Mechanics, Manufacturing and Functions
Abstract: Soft-hard material integration is ubiquitous in biological materials and structures in nature and has also attracted growing attention in the bio-inspired design of advanced functional materials, structures and devices. The inherent physical distinction between these soft and hard phases has led to fundamental differences in their mechanical behavior (e.g. usually more than two orders of magnitude difference in Young’s modulus) but is harnessed well in biological structures through elegant and facile integrated organizations with unprecedented functions as a whole. In this talk, I will present a theoretical mechanics framework that can describe the rotation of hard particles in a soft matrix subjected to a far-field stress. Strong couplings and competitions of the rotation of hard particles among each other will be discussed in parallel with validations from extensive finite element analyses. I will also exemplify the design and manufacturing of soft-hard material enabled two functional structures and demonstrate their mechanically tunable functions by taking advantage of the rotation of hard particles.
October 3, 2018
Speaker: Prof. Xiaodong (Chris) Li, Department of Mechanical and Aerospace Engineering
Title: Nature's Design Wisdom and Additive Manufacturing
Abstract: Recent discoveries in seashells unveil that nature uses multiscale design strategies to achieve exceptional mechanical properties which are still beyond the reach of many engineering materials. The multiscale hierarchical structure, ranging from micro lamellae down to nanoparticles, renders seashells multilevel strengthening and toughening mechanisms such as crack deflection, interlocking, lamellae's deformability, biopolymer's viscosity, nanoparticle rotation, deformation twining in nanoparticles, and amorphization, jointly contributing to seashell's ultra-high mechanical robustness. To realize nature's performance in engineering materials, we need to intelligently design and select materials. This talk will present several case studies in which nature's multiscale design strategies and materials selection principles are applied through additive manufacturing.
October 10, 2018
Speaker: Prof. David Green, Departments of Materials Science and Chemical Engineering
Title: Detection, Prediction, and Visualization of Ligand Phase Separation on Metal Nanoparticles
Abstract: Our research drives vital innovation in the realm of nanoparticle surface engineering, which has applications in a broad range of fields including cancer treatment and energy conversion. Our objective is to push the limits of nanoscience to characterize, visualize, and model the subnanometer-ordered domains in the ligand shells on nanoparticles (NPs), which has been demonstrated to increase the efficiencies of cell penetration and catalytic reactions. The combinations of the experimental and theoretical methodologies, which involve the integration of laser desorption/ionization mass spectroscopy (LDI-MS), transmission electron microscopy (TEM), and molecular simulation, are unprecedented. We demonstrate the techniques with silver NPs functionalized with dodecanethiol (DDT) and one other ligand from a series alkanethiol homologues ranging from deuterated dodecanethiol (DDT[D25]) down to butanethiol. Further, monolayers were formulated from mixtures of DDT and 2-mercaptoethanol (2-ME). The physical and chemical differences between the ligands dictate their distribution in the monolayer over well-mixed, stripe, and Janus (or hemispherically phase-separated) morphologies. We are furthering this research to expedite the development of new structure-property paradigms for the creation of materials that have only been realized in simulation.
October 24, 2018
Speaker: Prof. Stefanie Redemann, Department of Molecular Physiology and Biological Physics
Title: Mechanics of Spindle Assembly
Abstract: Microtubule based spindles are a complex three-dimensional apparatus that functions to ensure faithful segregation of chromosomes during cell division in mitosis and meiosis. Our current understanding of spindle architecture is mainly based on a plethora of information derived from light microscopy with rather few insights about spindle ultrastructure obtained from 3D electron microscopy. Recently, serial-section electron tomography has delivered detailed reconstructions of complete mitotic and meiotic spindles in the early C. elegans embryo (Redemann et al., 2017). Based on the large-scale reconstructions, we were able to identify each individual microtubule and obtain detailed spatial information on length, interactions and deformations. By combining electron tomography of serial sections with light microscopy and mathematical modelling we attempt to develop a holistic model of spindle assembly, mechanics and forces during chromosome segregation in mitosis and meiosis.
October 31, 2018
Speaker: Prof. Thomas H. Barker, Department of Biomedical Engineering and Cell Biology
Title: Cells and their matrix: a struggle for power
Abstract: Increasingly, the extracellular matrix (ECM) microenvironment is appreciated as a potent instructor of cell phenotype. Recent examples that highlight the role of ECM in directing tissue homeostasis and disease include tumor stroma that instruct metastasis and ECM mechanics that drive the differentiation of pro-fibrotic myofibroblasts. My lab has focused on the dynamic reciprocity between mesenchymal stroma cells (fibroblasts), the arbiter of tissue remodeling, and their extracellular matrix microenvironment. Recent findings from the lab suggest there are far greater complexities in fibroblast-matrix communication than previously thought. I will present multiple vignettes from our recent work that shed light on how cells sense and respond to elevated matrix stiffness and how chemical modifications to the ECM change the rules of engagement and add another level of complexity to cell-matrix homeostasis in the context of aging and disease.
November 7, 2018
Speaker: Prof. Liheng Cai, Departments of Materials Science and Chemical Engineering
Title: Squishy Materials: From Watery Extracellular Matrices to Soft yet ‘Dry’ Gels
Abstract: Natural extracellular matrices and synthetic polymer gels are dramatically different, but their properties and functions are largely determined by structure and architecture of their common component polymers. Such a deterministic correlation poses opportunities emerging at the interface of polymer science and biology. In this talk, I will discuss how knowledge in polymer science enables new understanding of biological questions and design of new soft materials. I will present the discovery of a brushlike extracellular matrix in the human airway. This biopolymer brush protects our lungs from inhaled infectious particulates. Inspired by the biopolymer brush, we synthesize a polymer network by crosslinking bottlebrush rather than linear polymers. We find that the brushlike architecture prevents the formation of entanglements, enabling an extremely soft yet ‘dry’ gel with prescribed elastic moduli mimicking that of ‘watery’ biological tissues. Moreover, we show that using stimuli reversible crosslinks such ‘dry’ gels become a new type of inks for 3D printing. I will also discuss applications and scientific challenges stimulated by these discoveries.
November 14, 2018
Speaker: Prof. Thomas A. Platts-Mills, Department of Medicine and Microbiology, Chief of Division of Asthma, Allergy and Immunology
Title: The Alpha-Gal Syndrome as a Consequence of Bites From The Lone Star Tick
Abstract: In large areas of the United States, the lone star tick Amblyomma americanum has increased dramatically because of the increase in the deer population which is the primary breeding host for this tick. The lone stars are known vectors for several diseases, but recently it has been shown that bites from larval or adult ticks can induce sensitization to an important oligosaccharide of the non-primate mammals. This sensitization can be identified by an in vitro assay for IgE to galactose alpha-1, 3-galactose (alpha-gal). The presence of this antibody was first recognized because of severe reactions to the monoclonal antibody cetuximab. However, equally significant, it is now clear that sensitized subjects can experience delayed anaphylaxis 2-5 hours after eating red meat. This form of delayed reactivity was initially difficult to diagnose. It is now clear that the combination of reactions starting in adult life, the characteristic delay after eating red meat and a positive blood test, is sufficient to diagnose the condition. Furthermore, in these cases a diet avoiding red meat is effective in 90% of cases in preventing further severe attacks. Strikingly, bites of these ticks that are related to sensitization produce severe and prolonged itching at the site, which is very different from the experience with bites from Ixodes scapularis. Although the lone star tick routinely carries Rickettsia amblyomii, there is very little evidence that the sensitization to the oligosaccharide is caused by symbionts.
November 28, 2018
Speaker: Prof. Marija Vucelja, Department of Physics
Title: Thermal relaxations and the Mpemba effect
Abstract: The Mpemba effect is a phenomenon when "hot can cool faster than cold" - a “shortcut” in relaxation to thermal equilibrium. It occurs when a physical system initially prepared at a hot temperature, cools faster than an identical system prepared at a colder temperature. The effect was discovered as a peculiarity of water. Despite following observations in granular gasses, magnetic alloys, and spin glasses, the effect is still most often referred to as an “oddity” of water, although it is widespread and general.
December 5, 2018
Speaker: Prof. Douglas W. DeSimone, Department of Cell Biology
Title: Understanding the Adhesive and Mechanical Forces that Assemble and Shape Tissues
Abstract: Morphogenesis is the fundamental developmental process that drives tissue assembly and elaborates the diverse anatomical structures that together comprise the body plans of all metazoa. Most human birth defects arise from disruptions in normal morphogenetic processes. How morphogenesis works at multiple levels of organization and complexity is one of the key remaining questions in biology and progress in this area will be needed to help inform efforts to engineer replacement tissues and organs. For nearly three decades our laboratory has approached this problem by focusing on the cell movements and tissue rearrangements responsible for gastrulation in the amphibian Xenopus. We explore how cell adhesion to other cells and to the extracellular matrix (ECM) is regulated to promote or stabilize the cell and tissue movements of gastrulation. Cadherin and integrin adhesion complexes are central players in these processes and aside from their general roles in holding cells and tissues together, they also sense, resist and distribute mechanical forces that arise as a consequence of morphogenesis. We have discovered a novel function for cadherins and keratin intermediate filaments (KIFs) in the force-dependent regulation of collective cell migration in the mesendoderm at gastrulation. Although the importance of adherens junctions, focal adhesions and the actin cytoskeleton to mechanosensation and mechanotransduction is now well established, the role of desmosomes and other intermediate filament associated junctions in these processes has been largely overlooked. A major goal of our current work is to bridge this significant gap in understanding by focusing on intermediate filament functions and the association of the KIF cytoskeleton with cadherin-based adhesions in collectively migrating cells.
January 16, 2019
Speaker: Dr. David Shook, Department of Cell Biology
Title: Biomechanics of Morphogenesis
Abstract: Morphogenic movements are driven by forces generated by embryonic cells, integrated at the tissue level as “morphogenic machines”. Within the biomechanical context of the embryo, these machines give rise to global shape change and re-organization. I will describe my recent characterization of one such machine operating in amphibians, Convergent Thickening (CT) and our understanding of the biomechanics involved. CT is expressed in a ring of tissue just below the equator of the spherical embryo, and is involved in generating forces that pull the top half of the embryo down and push the bottom half of the embryo inside. Our evidence suggests that CT is driven by changes in the surface tension of this tissue. This is supported by observations of tissue behavior and measurements of tissue surface tension and convergence forces. I will also describe recent observations about the biomechanical properties of a second machine, mesendoderm migration, and discuss how they may play a role in its morphogenesis. The integration of this machine with the movements of the embryo as a whole during gastrulation will be discussed, as well as planned approaches to further elucidate the biomechanical and molecular basis of these movements.
January 23, 2019
Speaker: Prof. Rachel A. Letteri, Department of Chemical Engineering
Title: Forming Sticky Droplets from Slippery Polymer Zwitterions
Abstract: After introducing work we’re starting in our lab on molecular ‘VELCRO®’ strips and new polymer (bio)materials, this talk will describe squishy, sticky emulsion droplet networks constructed from slippery polymer zwitterions (work from my PhD). While polymer zwitterions, with both a positive and a negative charge on each repeating unit, are typically regarded as non-interactive and slippery materials, here they promote adhesion between oil-in-water droplets, producing solid-like droplet networks. Changing the salt concentration, temperature, and other factors (e.g., concentration of reactive additives) modulates adhesion between droplets and the macroscopic properties of the corresponding networks. These interactions persist under flow in microfluidic devices and upon extrusion into responsive supracolloidal fibers. Given the highly tunable properties and scalability of polymers, and the biocompatibility and unique stimuli-responsive behavior of polymer zwitterions, these composites offer ample opportunities as engineering and biomaterials, and components thereof, from 3D printing inks to self-healing fibers, among others.
January 30, 2019
Short talk. Speaker: Matthew Diasio (Green Group)
Title: Liquid-Phase Shear Exfoliation and Dispersion of Graphene: Colloid Theory Approaches to Production and Characterization
Abstract: Liquid-phase exfoliation of graphite is an economical and increasingly popular method of graphene production. Shear exfoliation processes have achieved some of the highest production rates of few-layer graphene and show great promise for industrial scale up. Successful applications of graphene dispersions depend on the colloidal stability of these systems over practical time scales and under stresses experienced during processing and use. However, attempts at predicting the exfoliation and dispersion stability of graphene in a variety of liquids are still limited. Based on classical colloid theory, we propose evaluating candidate exfoliation liquids on their viscosity and dielectric properties to improve yield and stability and present the results of exfoliation in a novel solvent.
Long talk. Speaker: Prof. Steven Caliari, Department of Chemical Engineering and Biomedical Engineering
Title: Squishy Materials for Skeletal Muscle Tissue Engineering
Abstract: Skeletal muscle injuries and diseases are pervasively common in patients of many backgrounds ranging from elite athletes and soldiers to the elderly. Despite the ability of skeletal muscle to repair itself following smaller injuries, there are a variety of traumatic injuries and disorders that result in an irrecoverable loss of muscle mass and function, termed volumetric muscle loss (VML). Our groups engineers instructive biomaterials with tailored biophysical and biochemical properties to combat this serious human health challenge. In this talk we will discuss our progress on two biomaterials approaches we are taking: 1) Engineering of conductive 3D collagen-based scaffolds with highly aligned, anisotropic pores, and 2) Supramolecularly-assembled shear-thinning and self-healing hyaluronic acid hydrogel nanofibers.
February 6, 2019
Speaker: Prof. Chris Highley, Department of Biomedical Engineering and Chemical Engineering
Title: Designing hydrogel systems to address challenges in extrusion-based bioprinting
Abstract: 3D printing (3DP) technologies have received great interest in biomedical applications. They offer the potential to fabrication patient-specific products and the capability to use computer-controlled hardware in the creation of tissue engineered constructs that recapitulate biological structure and function. In the application of 3DP technologies to tissue engineering, in the area of work referred to as “bioprinting”, there remain significant challenges that must be addressed. Among these challenges are those that are shared with the broader field of tissue engineering, such as how to print vessel-like channels within tissue constructs to support living cells, or how to achieve high-resolution heterogeneity of cells and materials within the construct that may be necessary to achieving biomimetic function. There are also challenges specific to the bioprinting itself, such as printing soft, hydrogel materials that are well-established in tissue engineering, but often difficult to print, because of competing requirements of ink flow and stability in a printing process. In this talk, I will present work on two hydrogel systems which are designed to address these challenges in extrusion-based bioprinting. In a first material system, hydrogel crosslinking was designed to enable shear-thinning and self-healing behaviors that allowed for both the printing of a hydrogel ink, but also the use of that hydrogel as a support into which cells, materials, and void spaces (channels) could be printing. In the second system, hydrogel materials were formulated as microparticles in a jammed, granular material that offered viscoelastic properties well-suited to 3DP and the potential to serve as a means of printing many previous unprintable hydrogel and soft materials.
February 13, 2019
Speaker: Prof. Edward H. Egelman, Department of Biochemistry and Molecular Genetics
Title: Cryo-EM of Helical Protein and Nucleoprotein Polymers at Near-Atomic Resolution
Abstract: Large amounts (sometimes the majority) of protein in eukaryotic, bacterial and archaeal cells is often found in the form of helical polymers. Viruses infecting these cells can also be helical. We have been using electron cryo-microscopy (cryo-EM) to study the structure and function of many of these polymers. Since the introduction of direct electron detectors into transmission electron microscopes about six years ago, there has been a “resolution revolution” in cryo-EM where near-atomic levels of resolution can now almost routinely be achieved for many macromolecular complexes. While some of these complexes can, in principle, be crystallized, cryo-EM has emerged as the method of choice for structural studies of such complexes as it does not require crystallization, uses far less sample, and is much faster. But for helical polymers most can never be crystallized and cryo-EM is not only the preferred method but the only method available for reaching near-atomic resolution. I will describe applications of cryo-EM to a range of systems, from viruses that infect organisms living in nearly boiling acid, to an archaeal pilus that is nearly indestructible, to “microbial nanowires” that conduct electrons. All of these studies provide not only new understanding of biology and evolution, but yield insights into novel structures that can have applications to drug delivery, biomedical engineering and nanotechnology.
February 20, 2019 (canceled because of snow)
Speaker: Prof. Kyle Lampe, Department of Chemical Engineering, Biomedical Engineering and Neuroscience
Title: Synthetic, Protein, and Hybrid Hydrogels as 3D Microenvironments for Neural Tissue Engineering
Abstract: Neural regeneration within the central nervous system (CNS) is a critical unmet challenge as brain and spinal cord disorders continue to be the leading cause of disability nationwide. Engineering microenvironments conducive to stem cell guidance and neural cell growth in vitro and therapeutic regeneration in vivo can be addressed with hydrogel materials that mimic native neural tissue. Designer multifunctional materials are well-suited as they support independent tuning of multiple biochemical and biophysical properties and allow three-dimensional (3D) encapsulation of neural cells to create a physiologically relevant engineered extracellular matrix. We use a variety of both synthetic and recombinant protein building blocks to create tunable 3D hydrogels. Our hydrogels are based on synthetic polymers like poly(ethylene glycol) and recombinant elastin-like proteinz (ELPz). By carefully tuning the degradation rate, integrin-binding ligand density, elastic modulus, and mixing of the two polymers, we create designer materials that highlight the utility of both proteins and synthetic polymers. By doing so, we engineer cell instructive and cell-responsive elements to directly influence stem cell differentiation and self-renewal. Our current work applies these concepts to the myelin-producing oligodendrocytes of the CNS, and their precursors, in an effort to enhance their maturation and therapeutic utility.
March 6, 2019
Speaker: Prof. Don Griffin, Department of Biomedical Engineering Department and Chemical Engineering
Title: Microporous Annealed Particle Scaffold: Creating a Blank Slate
Abstract: The default host reaction to a biomaterial implant is a foreign body response (FBR) that prevents functional interaction of the implant with surrounding tissue. FBR is an immune-mediated tissue response typified by rapid accumulation of immune cells and fibrotic tissue encapsulation. We work with a platform technology, Microporous Annealed Particle (MAP) scaffold, that was originally developed for acute wound healing and demonstrated a striking ability to promote tissue integration with minimal immune response. We have seen similar responses in two other animal models (stroke repair and subdermal implants) and believe that this platform shows great promise for complex tissue development in vivo and in vitro. Our lab focuses on using the MAP platform to study the impact of surface chemistry, microenvironment heterogeneity, and gradient formation on regenerative medicine and tissue engineering applications. More specifically, we focus on the use of highly-defined synthetic chemistry to provide a robust, translational approach.
March 20, 2019
Speaker: Prof. Peter Kasson, Departments of Molecular Physiology and Biological Physics and of Biomedical Engineering, University of Virginia, and Program in Molecular Biophysics, Uppsala University
Title: Membrane organization and deformation in enveloped virus entry
Abstract: Enveloped viruses infect cells by binding to and fusing with cellular membranes. We have shown that the spatial organization of these interacting membranes can be key to infectious outcomes. Cholesterol content is key to the infectivity of many viruses; we show for influenza that it plays an unexpected molecular role in organizing membrane components. Membrane deformation is also a necessary step of enveloped viral entry, but the mechanistic roles of membrane intermediates are difficult to probe directly in physiological fusion. We use single-virus fusion kinetics and molecular simulations as a window into the mechanisms of infection, identifying off-pathway states that are targets for antivirals and developing physical tools to disentangle the roles of viral binding, protein activation, and membrane bending in viral entry.
March 27, 2019
Speaker: Prof. Matthew Lazarra, Departments of Chemical Engineering and Biomedical Engineering
Title: Use of "squishy materials" in the study of cancer biology and cancer response to therapy
Abstract: While a great deal of cancer research begins in plastic cell culture dishes with transformed tumor cells cultured in a two-dimensional monolayer, real tumors are three-dimensional structures that interact with a complex and dynamically changing stroma, consisting of a multi-component extracellular matrix and non-cancer supporting cells (e.g., tumor-associated fibroblasts and macrophages). This talk will focus on: (1) our recent studies of the ability of tumor cells to form three-dimensional squishy structures and (2) the ability of tumor cells to interact with different squishy materials, including synthetic hydrogels engineered to mimic certain aspects of the tumor microenvironment and intact tissues isolated from animals or human tumors. These studies are helping us to understand the relevance of our basic findings from conventional cell culture studies to the in vivo setting and will thus play a role in the eventual translation of our work to the clinic.
April 3, 2019
Speaker: Prof. Melissa Kendall, Department of Microbiology, Immunology, and Cancer Biology
Title: Bacterial strategies for host sensing and virulence regulation
Abstract: Chemical and nutrient signaling are fundamental for all cellular processes, including interactions between the mammalian host and the microbiota, which have a significant impact on health and disease. My lab is interested in understanding how bacterial pathogens exploit chemical and nutrient signaling to precisely regulate virulence gene expression to establish infection and cause disease. Elucidating these processes may enhance our arsenal of tools, such as new therapies or vaccines, to combat infectious diseases. This talk will describe how enteric pathogens integrate metabolite- and oxygen-sensing to control expression of virulence determinants that influence pathogenesis and interactions with the host.
April 24, 2019
Speaker: Prof. Xiaorong Liu, Department of Biology
Title: Neural Damage in Glaucoma
Abstract: I have been interested in understanding the regulation and misregulation of retinal structures and functions during normal development and in diseased conditions. My laboratory mainly has two lines of research: one is to investigate the normal development and function of retinal ganglion cells (RGCs), and the other to examine how visual system degenerates in mouse models of glaucoma. The former studies on RGC development provides us unique and innovative tools for the latter one to characterize the early structural and functional alteration of RGCs in glaucoma, which is much needed to advance the field. Glaucoma is a major cause of blindness characterized by progressive RGC death and vision loss. There is no cure because RGC loss is irreversible. Therefore, it is critical to understand how RGCs degenerate and die with glaucoma development and progression. We have established different animal models of glaucoma to investigate RGC death and its underlying mechanisms. For example, we are one of the first to show that the structural and functional degeneration of RGCs is subtype-dependent, and that brain-derived neurotrophic factor (BDNF) protects RGCs in a type-dependent manner. We are further examining the early degeneration of RGCs in order to establish a novel biomarker for clinical detection of the disease.
May 1, 2019
Speaker: Prof. Sen Zhang, Department of Chemistry
Title: Controlling Multiscale Cooperation at Nanocrystals Surfaces and Interfaces for Enhanced Electrocatalysis
Abstract: Catalysis at surfaces and interfaces where there exists bi- or multi-component cooperation has been identified as crucial for many processes related to energy and environmental applications. In this talk, I will highlight such cooperative catalysis can be synthetically controlled at nanometer and singe-atom scale over well-defined nanocrystals, and can play critical roles in maximizing the benefit of oxygen-mediated energy conversion reactions: oxygen reduction reaction (ORR) for fuel cells and oxygen evolution reaction (OER) for water electrolyzer. The first example is M-Pt (M=non-precious metals) core-shell nanocrystals within which desirable/undesirable interfaces between non-precious metal M core and precious metal Pt shell are identified by density functional theory (DFT) calculations and are practically balanced by nanocrystal synthesis. The optimized core-shell nanocrystals exhibit favorable interfacial interaction at nanometer scale through properly coupled electronic and strain effects, leading to an enhanced electrocatalytic efficiency toward oxygen reduction reaction (ORR). In second example, we take advantage of single-atom Co's synergy with various oxide support for electrochemical oxygen evolution reaction (OER). By choosing the proper oxide supporting nanocrystals, single atom Co conversion and stabilization at high valence OER active site can be controlled through its interaction with supporting materials. The relevant theoretical calculation, controlled synthesis and structural/catalytic characterization of nanocrystals will be discussed.
September 18, 2019
Speaker: Prof. Kateri H. DuBay, Department of Chemistry
Title: Modeling self-organization within spatially and temporally variant
Abstract: Nanoscale self-assembly arises from and is highly sensitive to interactions among the assembling components and between them and their environment. Environmental complexities, such as spatial and temporal heterogeneities, are ubiquitous in self-assembling biological systems and materials processing protocols, yet our understanding of how they influence the assembly process remains limited. Our group uses numerical simulations to investigate how particles self-organize within these complex environments. Specifically, this talk will describe our investigations into the self-assembly of mixed ligand monolayers on the surfaces of faceted nanoparticles, the self-assembly of viral capsids within oscillatory environments, and the emergent self-organization of nascent oligomers during step-growth copolymerizations.
October 2, 2019
Speaker: Prof. Kyle J. Lampe, Department of Chemical Engineering
Title: Synthetic, Protein, and Hybrid Hydrogels as 3D Microenvironments for Neural Tissue Engineering
Abstract: Neural regeneration within the central nervous system (CNS) is a critical unmet challenge as brain and spinal cord disorders continue to be the leading cause of disability nationwide. Engineering microenvironments conducive to stem cell guidance and neural cell growth in vitro and therapeutic regeneration in vivo can be addressed with hydrogel materials that mimic native neural tissue. Designer multifunctional materials are well-suited as they support independent tuning of multiple biochemical and biophysical properties and allow three-dimensional (3D) encapsulation of neural cells to create a physiologically relevant engineered extracellular matrix. We use a variety of both synthetic, peptide, and recombinant protein building blocks to create tunable 3D hydrogels. For this talk, our hydrogels are based on synthetic polymers like poly(ethylene glycol) and recombinant elastin-like proteins (ELPs). By carefully tuning the degradation rate, integrin-binding ligand density, elastic modulus, and mixing of the two polymers, we create designer materials that highlight the utility of both proteins and synthetic polymers. By doing so, we engineer cell instructive and cell-responsive elements to directly influence stem cell differentiation and self-renewal. Our current work applies these concepts to the myelin-producing oligodendrocytes of the CNS, and their precursors, in an effort to enhance their maturation and therapeutic utility.
October 30, 2019
Speaker: Prof. Huiwang Ai, Department of Molecular Physiology and Biological Physics
Title: Imaging Bioactivity with Fluorescent and Bioluminescent Biosensors
Abstract: To date, bioluminescent reporters used in laboratories are mostly derivatives of two major luciferase families: ATP-dependent insect luciferases and ATP-independent marine luciferases. Despite that ATP-dependent luciferase-luciferin pairs have been widely used for in vivo bioluminescence imaging (BLI), they consume ATP for photon production and this metabolic disruption issue cannot be addressed by simply improving ATP-dependent bioluminescent reporters. Moreover, any bioluminescent biosensors derived from ATP-dependent luciferase-luciferin pairs are also intrinsically ATP-dependent. On the other hand, ATP-independent marine luciferase-luciferin pairs, such as NanoLuc-furimazine, have found broad applications in vitro, but they are far from optimal for in vivo BLI due to their blue emission and low photon penetration depth in tissue, poor substrate solubility and stability, and/or low substrate permeability through the blood-brain barrier (BBB). My talk will discuss our recent progress in the development of ATP-independent luciferase-luciferin pairs with greatly enhanced biocompatibility, robustness, and in vitro and in vivo sensitivity. I will further present our results on various fluorescent and bioluminescent biosensors.
November 6, 2019
Speaker: Holly M. Mayton(Berger Group), Nicholas Cornell (Griffin Group)
Title: Reducing bacterial biofilms with an engineered enzyme (Holly M. Mayton)
Abstract: Biofilm formation is a major cause of microbial persistence on food surfaces, medical devices, and dental implants because the biofilm matrix has been shown to provide pathogens and other bacteria with protection from common disinfection approaches. The potential of an enzyme-based biocide has been investigated as a supplement to common disinfection practices for preventing bacterial adhesion and removing mature biofilms. Crystal violet staining of biofilms formed in multi-well polystyrene plates has been used to demonstrate the efficacy of enzymatic biofilm prevention and removal on E. coli O157:H7, E. coli 25922, Salmonella Typhimurium, and Listeria monocytogenes. In the presence of 0.1 mg/mL enzyme, biofilm development was significantly inhibited for all bacteria, with a maximum of 41 ± 7% reduction for E. coli O157:H7. Effectiveness of mature biofilm removal varied by bacteria species type, with a maximum of 35 ± 12% reduction for E. coli O157:H7. A microfluidic flow cell was used to directly observe and quantify the impact of enzyme rinses on E. coli O157:H7 cells adhered to spinach leaf surfaces. In the flow cell, enzyme rinses resulted in significantly greater cell removal than water, representing a reversal of initial phases of biofilm formation. The homology of the enzyme employed in this work is similar to that of other glycosyl hydrolases; therefore, it is hypothesized that the enzyme plays a role in the direct degradation of extracellular polymers. Electron microscopy of treated and untreated cells reveal major modification to surface polysaccharide structures. Additionally, changes in cell surface hydrophobicity were measured using the microbial adhesion to hydrocarbons (MATH) test and provide further evidence of changes to the cell surface. These results present a strong case for further development and optimization of enzyme activity to be applied as an organic additive for minimizing food safety risks and clinical infections associated with biofilms.
Title: Variable Immobilization of Glycosaminoglycans for Controlled Biomaterial-Protein Interaction (Nicholas Cornell)
Abstract: Glycosaminoglycans (GAGs), such as chondroitin sulfate (CS) and heparin, are naturally occurring linear polysaccharides that regulate both homeostasis and wound healing. Specifically, GAGs are found throughout the extracellular matrix and interact with soluble proteins (e.g. growth factors) through electrostatic interactions with downstream regulation of cell signaling and behavior. The strength of these interactions is heavily influenced by the structural flexibility of the GAG to conform to proteins. Diabetic wounds, a particularly challenging class of skin wound, present numerous hurdles to effective tissue regeneration, including both pathologically low levels of GAGs. Previously, GAGs have been incorporated into wound healing biomaterials as highly modified polymeric backbones, however we hypothesize that this manner of incorporation greatly reduces their conformational freedom and, subsequently, their bioactivity. Our lab is interested in immobilizing GAGs within our biomaterial platform in a manner which more closely resembles the body’s natural linear presentation. We have developed two distinct forms of GAGs which can be easily incorporated within our Microporous Annealed Particle (MAP) platform technology. Our biomolecular investigations have revealed that the extent of GAG modification affects both the strength of protein-GAG and protein-biomaterial interactions.
November 20, 2019
Speaker: Prof. Sergei A. Egorov, Department of Chemistry
Title: Isotropic-Nematic Behavior of Semiflexible Polymers in the Bulk and under Confinement
Abstract: Density functional theory will be presented that is suitable for studying the isotropic-nematic phase transition of semiflexible polymers both in the bulk and under planar confinement. The effects of the density and temperature, as well as chain length and chain stiffness on the bulk phase diagram will be analyzed. The phenomenon of capillary nematization in a slit geometry will be discussed. The predictions of Density Functional Theory will be compared with previous theories and with extensive Molecular Dynamics simulations.
December 4, 2019
Speaker: Prof. Ku-Lung (Ken) Hsu, Department of Chemistry
Title: Chemical Biology and Chemistry for Translational Lipid Biology and Beyond
Abstract: Lipids represent a rich model system for understanding how nature maintains cellular architecture (membrane building blocks), bioenergetics (energy stores), and communication (secondary messengers) through fine adjustments in enzyme metabolism. Embedded within lipid structures is chemical information that define their metabolic fate and function. Elucidating structure-function relationships of lipids in biological systems has been traditionally challenging because of the massive structural diversity of lipids in nature and lack of tools to selectively probe their function in vivo. I will describe efforts from my group to use chemical biology and mass spectrometry to gain fundamental insights into diacylglycerol (DAG) biology and the translational potential of modulating DAG pathways in inflammation and immuno-oncology.