Physics Commons^™

Vimentin Takes A Hike – Emerging Roles Of Extracellular Vimentin In Cancer And Wound Healing, Sepideh Parvanian, Leila S. Coelho-Rato, Alison E. Patteson, John E. Eriksson

Physics - All Scholarship

Vimentin is a cytoskeletal protein important for many cellular processes, including proliferation, migration, invasion, stress resistance, signaling, and many more. The vimentin-deficient mouse has revealed many of these functions as it has numerous severe phenotypes, many of which are found only following a suitable challenge or stress. While these functions are usually related to vimentin as a major intracellular protein, vimentin is also emerging as an extracellular protein, exposed at the cell surface in an oligomeric form or secreted to the extracellular environment in soluble and vesicle-bound forms. Thus, this review explores the roles of the extracellular pool of vimentin …

The Molecular Biophysics Of Extracellular Vimentin And Its Role In Pathogen–Host Interactions, Sepideh Parvanian, Leila S. Coelho-Rato, John E. Eriksson, Alison E. Patteson

Physics - All Scholarship

Vimentin, an intermediate filament protein typically located in the cytoplasm of mesenchymal cells, can also be secreted as an extracellular protein. The organization of extracellular vimentin strongly determines its functions in physiological and pathological conditions, making it a promising target for future therapeutic interventions. The extracellular form of vimentin has been found to play a role in the interaction between host cells and pathogens. In this review, we first discuss the molecular biophysics of extracellular vimentin, including its structure, secretion, and adhesion properties. We then provide a general overview of the role of extracellular vimentin in mediating pathogen-host interactions, with …

Antibacterial And Cytocompatible Ph-Responsive Peptide Hydrogel, Dona I. Edirisinghe, Areetha D'Souza, Maryam Ramezani, Robert J. Carroll, Quenten Chicón, Cheyene L. Muenzel, Jonathan Soule, Mary B. Monroe, Alison E. Patteson, Olga V. Makhlynets

Physics - All Scholarship

A short peptide, FHHF-11, was designed to change stiffness as a function of pH due to changing degree of protonation of histidines. As pH changes in the physiologically relevant range, G′ was measured at 0 Pa (pH 6) and 50,000 Pa (pH 8). This peptide-based hydrogel is antimicrobial and cytocompatible with skin cells (fibroblasts). It was demonstrated that the incorporation of unnatural AzAla tryptophan analog residue improves the antimicrobial properties of the hydrogel. The material developed can have a practical application and be a paradigm shift in the approach to wound treatment, and it will improve healing outcomes for millions …

Mechanobiology As A Tool For Addressing The Genotype-To- Phenotype Problem In Microbiology, Merrill E. Asp, Minh-Tri Ho Thanh, Subarna Dutta, Jessica A. Comstock, Roy D. Welch, Alison E. Patteson

Physics - All Scholarship

The central hypothesis of the genotype–phenotype relationship is that the phenotype of a developing organism (i.e., its set of observable attributes) depends on its genome and the environment. However, as we learn more about the genetics and biochemistry of living systems, our understanding does not fully extend to the complex multiscale nature of how cells move, interact, and organize; this gap in understanding is referred to as the genotype-to-phenotype problem. The physics of soft matter sets the background on which living organisms evolved, and the cell environment is a strong determinant of cell phenotype. This inevitably leads to challenges as …

Extracellular Vimentin Is Sufficient To Promote Cell Attachment, Spreading, And Motility By A Mechanism Involving N-Acetyl Glucosamine-Containing Structures, Robert Bucki, Daniel V. Iwamoto, Xuechen Shi, Katherine E. Kerr, Fitzroy J. Byfield, Lukasz Suprewicz, Karol Sklodowski, Julian Sutaria, Pawel Misiak, Agnieszka Z. Wilczewska, Sekar Ramachandran, Aaron Wolfe, Minh H. Thanh, Eli Whalen, Alison E. Patteson, Paul A. Janmey

Physics - All Scholarship

Vimentin intermediate !laments form part of the cytoskeleton

of mesenchymal cells, but under pathological conditions often

associatedwith in"ammation, vimentin !laments depolymerize as

the result of phosphorylation or citrullination, and vimentin

oligomers are secreted or released into the extracellular environment.

In the extracellular space, vimentin can bind surfaces of cells

and the extracellular matrix, and the interaction between extracellular

vimentin and cells can trigger changes in cellular functions,

such as activation of !broblasts to a !brotic phenotype. The

mechanism by which extracellular vimentin binds external cell

membranes and whether vimentin alone can act as an adhesive

anchor for cells is largely …

A Torsion-Based Rheometer For Measuring Viscoelastic Material Properties, Merrill E. Asp, Elise Jutzeler, Jakub Kochanowski, Katherine Kerr, Dawei Song, Sarthak Gupta, Robert Carroll, Alison E. Patteson

Physics - All Scholarship

Rheology and the study of viscoelastic materials are an integral

part of engineering and the study of biophysical systems. Tissue rheology is even

used in the study of cancer and other diseases. However, the cost of a rheometer is

feasible only for colleges, universities, and research laboratories. Even if a rheometer

can be purchased, it is bulky and delicately calibrated, limiting its usefulness to the

laboratory itself. The design presented here is less than a tenth of the cost of a

professional rheometer. The design is also portable, making it the ideal solution to

introduce viscoelasticity to high school students …

Dynamic Remodeling Of Fiber Networks With Stiff Inclusions Under Compressive Loading, Robert J. Carroll, Minh H. Thanh, Alison E. Patteson

Physics - All Scholarship

The ability of tissues to sustain and withstand mechanical stress is critical to tissue development and healthy tissue maintenance. The mechanical properties of tissues are typically considered to be dominated by the fibrous extracellular matrix (ECM) component of tissues. Fiber network mechanics can capture certain mechanical features of tissues, such as shear strain stiffening, but is insufficient in describing the compressive response of certain tissues and blood clots that are rich in extracellular matrix. To understand the mechanical response of tissues, we employ a contemporary mechanical model, a fibrous network of fibrin embedded with inert bead inclusions that preserve the …

How Green Lakes State Park Got Its Name: The Optics And Appearance Of Fayetteville Green Lakes, Eric A. Schiff

Physics - All Scholarship

The extraordinary and variable appearance of the Fayetteville Green Lakes in the spring, summer, and fall has been the subject of journalistic and scientific attention for more than 150 years. This article addresses the subject in two sections for differing readerships. The first section is a description of the essential science for a general readership. The second section is an abstract of the science for technically knowledgeable readers. The layout of the article is designed for a folded paper flier suitable for distribution to visitors to the lakes.

The article describes the three key properties of the lakes’ waters that …

Unique Role Of Vimentin Networks In Compression Stiffening Of Cells And Protection Of Nuclei From Compressive Stress, Katarzyna Pogoda, Fitzroy Byfield, Piotr Deptuła, Mateusz Cieśluk, Łukasz Suprewicz, Karol Skłodowski, Jordan L. Shivers, Anne Van Oosten, Katrina Cruz, Ekaterina Tarasovetc, Ekaterina L. Grishchuk, Fred C. Mackintosh, Robert Bucki, Alison E. Patteson, Paul A. Janmey

Physics - All Scholarship

In this work, we investigate whether stiffening in compression is a feature of single cells and whether the intracellular polymer networks that comprise the cytoskeleton (all of which stiffen with increasing shear strain) stiffen or soften when subjected to compressive strains. We find that individual cells, such as fibroblasts, stiffen at physiologically relevant compressive strains, but genetic ablation of vimentin diminishes this effect. Further, we show that unlike networks of purified F-actin or microtubules, which soften in compression, vimentin intermediate filament networks stiffen in both compression and extension, and we present a theoretical model to explain this response based on …

Spreading Rates Of Bacterial Colonies Depend On Substrate Stiffness And Permeability, Alison Patteson, Merrill Asp, Minh H. Thanh, Danielle A. Germann, Robert J. Carroll, Alana Franceski, Roy D. Welch, Arvind Gopinath

Physics - All Scholarship

The ability of bacteria to colonize and grow on different surfaces is an essential process for biofilm development. Here, we report the use of synthetic hydrogels with tunable stiffness and porosity to assess physical effects of the substrate on biofilm development. Using time-lapse microscopy to track the growth of expanding Serratia marcescens colonies, we find that biofilm colony growth can increase with increasing substrate stiffness, unlike what is found on traditional agar substrates. Using traction force microscopy-based techniques, we find that biofilms exert transient stresses correlated over length scales much larger than a single bacterium, and that the magnitude of …

Materials Science And Mechanosensitivity Of Living Matter, Alison E. Patteson, Merrill E. Asp, Paul A. Janmey

Physics - All Scholarship

Living systems are composed of molecules that are synthesized by cells that use energy sources within their surroundings to create fascinating materials that have mechanical properties optimized for their biological function. Their functionality is a ubiquitous aspect of our lives. We use wood to construct furniture, bacterial colonies to modify the texture of dairy products and other foods, intestines as violin strings, bladders in bagpipes, and so on. The mechanical properties of these biological materials differ from those of other simpler synthetic elastomers, glasses, and crystals. Reproducing their mechanical properties synthetically or from first principles is still often unattainable. The …

Rab11 Endosomes And Pericentrin Coordinate Centrosome Movement During Pre-Abscission In Vivo, Nikhila Krishnan, Maxx Swoger, Lindsay I. Rathbun, Peter J. Fioramonti, Judy Freshour, Michael Bates, Alison E. Patteson, Heidi Hehnly

Physics - All Scholarship

The last stage of cell division involves two daughter cells remaining interconnected by a cytokinetic bridge that is cleaved during abscission. Conserved between the zebrafish embryo and human cells, we found that the oldest centrosome moves in a Rab11-dependent manner towards the cytokinetic bridge sometimes followed by the youngest. Rab11-endosomes are organized in a Rab11-GTP dependent manner at the mother centriole during pre-abscission, with Rab11 endosomes at the oldest centrosome being more mobile compared with the youngest. The GTPase activity of Rab11 is necessary for the centrosome protein, Pericentrin, to be enriched at the centrosome. Reduction in Pericentrin expression or …

Vimentin Intermediate Filaments Mediate Cell Morphology On Viscoelastic Substrates, Maxx Swoger, Sarthak Gupta, Elisabeth E. Charrier, Michael Bates, Heidi Hehnly, Alison E. Patteson

Physics - All Scholarship

The ability of cells to take and change shape is a fundamental feature underlying development, wound repair, and tissue maintenance. Central to this process is physical and signaling interactions between the three cytoskeletal polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). Vimentin is an IF protein that is essential to the mechanical resilience of cells and regulates cross-talk among the cytoskeleton, but its role in how cells sense and respond to the surrounding extracellular matrix is largely unclear. To investigate vimentin’s role in substrate sensing, we designed polyacrylamide hydrogels that mimic the elastic and viscoelastic nature of in vivo tissues. …

Extracellular Vimentin As A Target Against Sars-Cov-2 Host Cell Invasion, Łukasz Suprewicz, Maxx Swoger, Sarthak Gupta, Ewelina Piktel, Fitzroy J. Byfield, Daniel V. Iwamoto, Danielle Germann, Joanna Reszeć, Natalia Marcińczyk, Robert J. Carroll, Paul A. Janmey, J. M. Schwarz, Robert Bucki, Alison E. Patteson

Physics - All Scholarship

Infection of human cells by pathogens, including SARS-CoV-2, typically proceeds by cell surface binding to a crucial receptor. The primary receptor for SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2), yet new studies reveal the importance of additional extracellular co-receptors that mediate binding and host cell invasion by SARS-CoV-2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens’ cellular uptake. Biophysical and cell infection studies are done to determine whether vimentin might bind SARS-CoV-2 and facilitate its uptake. Dynamic …

A Data-Driven Statistical Description For The Hydrodynamics Of Active Matter, Ahmad Borzou, Alison E. Patteson, J. M. Schwarz

Physics - All Scholarship

Modeling living systems at the collective scale can be very challenging because the individual constituents can themselves be complex and the respective interactions between the constituents may not be fully understood. With the advent of high throughput experiments and in the age of big data, data-driven methods are on the rise to overcome these challenges. Although machine-learning approaches can help quantify correlations between the various players, they do not directly shed light on the underlying physical principles of such systems. Here, we present a data-driven method for obtaining the phase-space density of active matter systems such that the solution to …

The Role Of Vimentin–Nuclear Interactions In Persistent Cell Motility Through Confined Spaces, Sarthak Gupta, Alison E. Patteson, J. M. Schwarz

Physics - All Scholarship

The ability of cells to move through small spaces depends on the mechanical properties of the cellular cytoskeleton and on nuclear deformability. In mammalian cells, the cytoskeleton is composed of three interacting, semi-flexible polymer networks: actin, microtubules, and intermediate filaments (IF). Recent experiments of mouse embryonic fibroblasts with and without vimentin have shown that the IF vimentin plays a role in confined cell motility. Here, we develop a minimal model of a cell moving through a microchannel that incorporates explicit effects of actin and vimentin and implicit effects of microtubules. Specifically, the model consists of a cell with an actomyosin …

Dynamic Nuclear Structure Emerges From Chromatin Cross-Links And Motors, Kuang Liu, Alison E. Patteson, Edward J. Banigan, J. M. Schwarz

Physics - All Scholarship

The cell nucleus houses the chromosomes, which are linked to a soft shell of lamin protein filaments. Experiments indicate that correlated chromosome dynamics and nuclear shape fluctuations arise from motor activity. To identify the physical mechanisms, we develop a model of an active, cross-linked Rouse chain bound to a polymeric shell. System-sized correlated motions occur but require both motor activity and cross-links. Contractile motors, in particular, enhance chromosome dynamics by driving anomalous density fluctuations. Nuclear shape fluctuations depend on motor strength, cross-linking, and chromosome-lamina binding. Therefore, complex chromosome dynamics and nuclear shape emerge from a minimal, active chromosome-lamina system.

Cell-Induced Confinement Effects In Soft Tissue Mechanics, Dawei Song, Jordan L. Shivers, Fred C. Mackintosh, Alison E. Patteson, Paul A. Janmey

Physics - All Scholarship

The mechanical properties of tissues play a critical role in their normal and pathophysiological functions such as tissue development, aging, injury, and disease. Understanding tissue mechanics is important not only for designing realistic biomimetic materials for tissue engineering and drug testing but also for developing novel diagnostic techniques and medical interventions. Tissues are heterogeneous materials consisting of cells confined within extracellular matrices (ECMs), both of which derive their structural integrity, at least in part, from networks of biopolymers. However, the rheology of purified reconstituted biopolymer networks fails to explain many key aspects of tissue mechanics. Notably, purified networks typically soften …

Vimentin Tunes Cell Migration On Collagen By Controlling Β1 Integrin Activation And Clustering, Zofia Ostrowska-Podhorodecka, Isabel Ding, Wilson Lee, Jelena Tanic, Sevil Abbasi, Pamma D. Arora, Richard S. Liu, Alison E. Patteson, Paul A. Janmey, Christopher A. Mcculloch

Physics - All Scholarship

Vimentin is a structural protein that is required for mesenchymal cell migration and directly interacts with actin, β1 integrin and paxillin. We examined how these interactions enable vimentin to regulate cell migration on collagen. In fibroblasts, depletion of vimentin increased talin-dependent activation of β1 integrin by more than 2-fold. Loss of vimentin was associated with reduction of β1 integrin clustering by 50% and inhibition of paxillin recruitment to focal adhesions by more than 60%, which was restored by vimentin expression. This reduction of paxillin was associated with 65% lower Cdc42 activation, a 60% reduction of cell extension formation and a …

Bacterial Activity Hinders Particle Sedimentation, Jaspreet Singh, Alison E. Patteson, Bryan O. Torres Maldonado, Prashant K. Purohit, Paulo E. Arratia

Physics - All Scholarship

Sedimentation in active fluids has come into focus due to the ubiquity of swimming micro-organisms in natural and industrial processes. Here, we investigate sedimentation dynamics of passive particles in a fluid as a function of bacteria E. coli concentration. Results show that the presence of swimming bacteria significantly reduces the speed of the sedimentation front even in the dilute regime, in which the sedimentation speed is expected to be independent of particle concentration. Furthermore, bacteria increase the dispersion of the passive particles, which determines the width of the sedimentation front. For short times, particle sedimentation speed has a linear dependence …

Cell Nuclei As Cytoplasmic Rheometers, Alison E. Patteson, J. M. Schwarz

Physics - All Scholarship

Some researchers probe the mechanics of cells by perturbing them from the outside, such as using an atomic force microscope probe to record the amount of deformation of the cell in response to applying a prescribed force at a defined speed. Other researchers probe the mechanics of cells by perturbing them from the inside, an example of which is particle-tracking microrheology, in which the spontaneous motion of submicron, passive fluorescent beads ballistically injected earlier into the cell decodes the cell moduli. Both types of probes are typically composed of nonliving material. In this issue of Biophysical Journal, Moradi and …

A Tissue-Engineered Human Trabecular Meshwork Hydrogel For Advanced Glaucoma Disease Modeling, Haiyan Li, Tyler Bagué, Alexander Kirschner, Ana N. Strat, Haven Roberts, Robert W. Weisenthal, Alison E. Patteson, Nasim Annabi, W. Daniel Stamer, Preethi S. Ganapathy, Samuel Herberg

Physics - All Scholarship

Abnormal human trabecular meshwork (HTM) cell function and extracellular matrix(ECM) remodeling contribute to HTM stiffening in primary open-angle glaucoma (POAG). Most current cellular HTM model systems do not sufficiently replicate the complex native three dimensional (3D) cell-ECM interface, limiting their use for investigating POAG pathology. Tissue-engineered hydrogels are ideally positioned to overcome shortcomings of current models. Here, we report a novel biomimetic HTM hydrogel and test its utility as a POAG disease model. HTM hydrogels were engineered by mixing normal donor-derived HTM cells with collagen type I, elastin-like polypeptide and hyaluronic acid, each containing photoactive functional groups, …

The Vimentin Cytoskeleton: When Polymer Physics Meets Cell Biology, Alison E. Patteson, Robert J. Carroll, Daniel V. Iwamoto, Paul A. Janmey

Physics - All Scholarship

The proper functions of tissues depend on the ability of cells to withstand stress and maintain shape. Central to this process is the cytoskeleton, comprised of three polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). IF proteins are among the most abundant cytoskeletal proteins in cells; yet they remain some of the least understood. Their structure and function deviate from those of their cytoskeletal partners, F-actin and microtubules. IF networks show a unique combination of extensibility, flexibility and toughness that confers mechanical resilience to the cell. Vimentin is an IF protein expressed in mesenchymal cells. This review highlights exciting new …

Mechanical And Non-Mechanical Functions Of Filamentous And Non-Filamentous Vimentin, Alison E. Patteson, Amir Vahabikashi, Robert D. Goldman, Paul A. Janmey

Physics - All Scholarship

Intermediate filaments (IFs) formed by vimentin are less understood than their cytoskeletal partners, microtubules and F-actin, but the unique physical properties of IFs, especially their resistance to large deformations, initially suggest a mechanical function. Indeed, vimentin IFs help regulate cell mechanics and contractility, and in crowded 3D environments they protect the nucleus during cell migration. Recently, a multitude of studies, often using genetic or proteomic screenings show that vimentin has many non-mechanical functions within and outside of cells. These include signaling roles in wound healing, lipogenesis, sterol processing, and various functions related to extracellular and cell surface vimentin. Extracellular vimentin …

Loops Versus Lines And The Compression Stiffening Of Cells, Mahesh C. Gandikota, Katarzyna Pogoda, Anne Van Oosten, Tyler A. Engstrom, Alison E. Patteson, Paul E. Janmey, J. M. Schwarz

Physics - All Scholarship

Both animal and plant tissue exhibit a nonlinear rheological phenomenon known as compression stiffening, or an increase in moduli with increasing uniaxial compressive strain. Does such a phenomenon exist in single cells, which are the building blocks of tissues? One expects an individual cell to compression soften since the semiflexible biopolymer-based cytoskeletal network maintains the mechanical integrity of the cell and in vitro semiflexible biopolymer networks typically compression soften. To the contrary, we find that mouse embryonic fibroblasts (mEFs) compression stiffen under uniaxial compression via atomic force microscopy studies. To understand this finding, we uncover several potential mechanisms for compression …

Loss Of Vimentin Enhances Cell Motility Through Small Confining Spaces, Alison E. Patteson, Katarzyna Pogoda, Fitzroy J. Byfield, Kalpana Mandal, Zofia Ostrowska-Podhorodecka, Elisabeth E. Charrier, Peter A. Galie, Piotr Deptuła, Robert Bucki, Christopher A. Mcculloch, Paul A. Janmey

Physics - All Scholarship

The migration of cells through constricting spaces or along fibrous tracks in tissues is important for many biological processes and depends on the mechanical properties of a cytoskeleton made up of three different filaments: F-actin, microtubules, and intermediate filaments. The signaling pathways and cytoskeletal structures that control cell motility on 2D are often very different from those that control motility in 3D. Previous studies have shown that intermediate filaments can promote actin-driven protrusions at the cell edge, but have little effect on overall motility of cells on flat surfaces. They are however important for cells to maintain resistance to repeated …

Vimentin Protects Cells Against Nuclear Rupture And Dna Damage During Migration, Alison E. Patteson, Amir Vahabikashi, Katarzyna Pogoda, Stephen A. Adam, Kalpana Mandal, Mark Kittisopikul, Suganya Sivagurunathan, Anne Goldman, Robert D. Goldman, Paul A. Janmey

Physics - All Scholarship

Mammalian cells frequently migrate through tight spaces during normal embryogenesis, wound healing, diapedesis, or in pathological situations such as metastasis. Nuclear size and shape are important factors in regulating the mechanical properties of cells during their migration through such tight spaces. At the onset of migratory behavior, cells often initiate the expression of vimentin, an intermediate filament protein that polymerizes into networks extending from a juxtanuclear cage to the cell periphery. However, the role of vimentin intermediate filaments (VIFs) in regulating nuclear shape and mechanics remains unknown. Here, we use wild-type and vimentin-null mouse embryonic fibroblasts to show that VIFs …

Emergence Of Tissue-Like Mechanics From Fibrous Networks Confined By Close-Packed Cells, Anne Van Oosten, Xingyu Chen, Likang Chin, Katrina Cruz, Alison E. Patteson, Katarzyna Pogoda, Vivek B. Shenoy, Paul A. Janmey

Physics - All Scholarship

The viscoelasticity of the crosslinked semiflexible polymer networks—such as the internal cytoskeleton and the extracellular matrix—that provide shape and mechanical resistance against deformation is assumed to dominate tissue mechanics. However, the mechanical responses of soft tissues and semiflexible polymer gels differ in many respects. Tissues stiffen in compression but not in extension1,2,3,4,5, whereas semiflexible polymer networks soften in compression and stiffen in extension6,7. In shear deformation, semiflexible polymer gels stiffen with increasing strain, but tissues do not1,2,3,4,5 …

Quenching Active Swarms: Effects Of Light Exposure On Collective Motility In Swarming Serratia Marcescens, Junyi Yang, Paulo E. Arratia, Alison E. Patteson, Arvind Gopinath

Physics - All Scholarship

Swarming colonies of the light-responsive bacteria Serratia marcescens grown on agar exhibit robust fluctuating large-scale flows that include arrayed vortices, jets and sinuous streamers. We study the immobilization and quenching of these collective flows when the moving swarm is exposed to intense wide-spectrum light with a substantial ultraviolet component. We map the emergent response of the swarm to light in terms of two parameters-light intensity and duration of exposure-and identify the conditions under which collective motility is impacted. For small exposure times and/or low intensities, we find collective motility to be negligibly affected. Increasing exposure times and/or intensity to higher …

Memory Formation In Matter, Joseph Paulsen, Nathan C. Keim, Zorana Zeravcic, Srikanth Sastry, Sidney R. Nagel

Physics - All Scholarship

Memory formation in matter is a theme of broad intellectual relevance; it sits at the interdisciplinary crossroads of physics, biology, chemistry, and computer science. Memory connotes the ability to encode, access, and erase signatures of past history in the state of a system. Once the system has completely relaxed to thermal equilibrium, it is no longer able to recall aspects of its evolution. The memory of initial conditions or previous training protocols will be lost. Thus many forms of memory are intrinsically tied to far-from-equilibrium behavior and to transient response to a perturbation. This general behavior arises in diverse contexts …