Bulletin of the American Physical Society
APS March Meeting 2023
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session F11: Mechanobiology of Cell-Matrix InteractionsFocus
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Sponsoring Units: DBIO Chair: Nadir Kaplan, Virginia Tech Room: Room 203 |
Tuesday, March 7, 2023 8:00AM - 8:36AM |
F11.00001: Mechanical heterogeneity and directional cues in the fibrous extracellular matrix Invited Speaker: Jacob Notbohm When cells contract or migrate within the three-dimensional extracellular matrix, they pull on the fibers surrounding them, generating displacements in the fibrous network. Though it is known that fibrous materials deform primarily by bending of fibers, the implications of fiber bending on the mechanics of the network are not fully clear. This is especially true for forces applied at small length scales, such as those of a cell. At these scales, typically tens of microns, the fiber network is highly random and nonlinear. This presentation will discuss experiments that quantify the mechanics of fibrous materials at small length scales under large deformations, like those induced by a contracting cell. Our experiments use microspheres made of poly(N-isopropylacrylamide), an active hydrogel that contracts when heated. With these particles, we can apply well-controlled displacements of large magnitude at scales of tens of microns. This presentation will demonstrate our use of these particles to quantify mechanical heterogeneity and anisotropy in matrices made of collagen fibers, with a key result being that the mechanics in random fiber networks are far more heterogeneous than often appreciated. This presentation will also describe use of these microspheres to study force-induced alignment and densification of fibers into distinct bands, similar in appearance to those that occur on the boundary of a tumor. Our experiments provide evidence that band formation results at least in part by an elastic phase transition resulting from an instability due to compression softening of the fiber network. |
Tuesday, March 7, 2023 8:36AM - 8:48AM |
F11.00002: Tutorial calculations for force-sensing proteins, catch bonding, and other elements of cell--matrix adhesion Philip Nelson The ability of cells to adhere to an extracellular matrix, exert forces on it, and in turn measure those forces is critical to many life processes. As the molecular details have emerged in recent years, they have proven to be quite complex. However, to a physicist, the key elements are familiar: They include entropic elasticity of polymers, catch-bonding, and two-state dynamics as cryptic binding sites pop open under force and hence become available for signaling interactions. Each of those processes can now be experimentally studied in vitro, without the complexity of a living cell. Students can observe all of those phenomena in simple kinetic simulations and compare them to experiment. Along the way, they also gain skills by implementing the stochastic simulation algorithm in a sequence of problems: * Simple Brownian motion; * Brownian motion with a linear potential landscape; * Brownian motion in a potential well with escape; * Brownian motion in a double-well potential, modeling a two-state system. Students directly observe the Einstein relation, emergence of the Boltzmann distribution, Kramers rates, the catch bonding phenomenon, and more. Although this exercise lacks the generality that we might get from a year of equilibrium and nonequilibrium statistical physics, it does illuminate key life processes in about two weeks of an undergraduate course. Most of this material is available in a recently published textbook. |
Tuesday, March 7, 2023 8:48AM - 9:00AM |
F11.00003: Mediating Cell Adhesion Using Surface Microtexture Caroline McCue, Kripa K Varanasi, Sean M Parks, Moony Tseng, Adel Atari There is a need for surfaces that lower cell adhesion strength while maintaining cell growth to enable the next generation of cell culture surfaces for delicate primary cells and automated, high throughput workflows. In this study, we investigated the use of microtexture alone to control cell adhesion. We developed a fast, simple, and inexpensive process for creating microtextured polystyrene surfaces. These cell culture surfaces enable decreased cell adhesion strength while maintaining high cell viability and proliferation, through a simple reduction in the cell-surface contact area. Cancer cells grown on microtextured polystyrene showed significant changes in cell morphology compared with cells grown on flat polystyrene. Using image analysis to quantify cell morphology changes, we found that surface textures decreased cell area by half and led to much more elongated cell shape compared to flat surfaces. We designed a microfluidic shear force measurement platform to quantify the removal of cells from these surfaces, and showed that significantly more cells were removed from the microtextured surfaces than the flat surfaces, demonstrating that our surfaces lead to decreased cell adhesion. |
Tuesday, March 7, 2023 9:00AM - 9:36AM |
F11.00004: Probing cell-matrix interactions in 3D at the local scale Invited Speaker: Ming Guo In this talk, I will introduce our recent works in quantitatively studying how cells interact with their surrounding extracellular matrix. In particular, I will discuss the critical impact of the matrix nonlinear elasticity in regulating cell-ECM mechanical interactions. For example, the nonlinear stiffening nature of the ECM enables a significantly extended stress dissipation, and the creation of a stiff shell surrounding the cell. These effects have an important role in regulating cell-cell communications, as well as the mechanobiology of cell-ECM interactions. In addition, I will also show results revealing the critical role of interfacial curvature on cell migratory behaviors. |
Tuesday, March 7, 2023 9:36AM - 9:48AM |
F11.00005: Local Nonlinear Elastic Response of Extracellular Matrices Haiqian Yang, Estelle Berthier, Chenghai Li, Pierre Ronceray, Yulong Han, Chase P Broedersz, Shengqiang Cai, Ming Guo Nonlinear stiffening is a ubiquitous property of major types of biopolymers that make up the extracellular matrices (ECM) including collagen, fibrin, and basement membrane. Within the ECM, many types of cells such as fibroblasts and cancer cells are known to mechanically stretch their surroundings that locally stiffens the matrix. Although the bulk nonlinear elastic behaviors of these biopolymer networks are well studied, their local mechanical responses remain poorly characterized. Here, to understand how a living cell feels the nonlinear mechanical resistance from the ECM, we mimic the cell-applied local force using optical tweezers; we report that the local stiffening responses in highly nonlinear ECM are significantly weaker than responses found in bulk rheology, across two orders of magnitude of the locally applied force since the onset of stiffening. With a minimal model, we show that a local point force application can induce a stiffened region in the matrix, which expands with increasing magnitude of the point force. Furthermore, we show that this stiffened region behaves as an effective probe upon local loading. The local nonlinear elastic response can be attributed to the nonlinear growth of this effective probe that linearly deforms an increasing portion of the matrix. |
Tuesday, March 7, 2023 9:48AM - 10:00AM |
F11.00006: Engineering Dynamic Cell-Material Interfaces to decode How Cells Communicate with Their Environment Ronit Freeman The extracellular matrix (ECM) is a complex physical network composed of multiple molecular constituents (proteins, proteoglycans, growth factors) that collectively regulate biological behavior in a highly dynamic interplay with cells. A major challenge in matrix biology is to understand how ECM dynamics may contribute to cell fate. To meet this challenge, there is a need for scaffolds whose properties change temporally in a predictable, programmable, or even responsive manner and enable the dynamic display of cues to cells. I will discuss the development of DNA/peptide-based stimuli-responsive interfaces as in vitro model systems able to recapitulate the dynamic cell-matrix interface. I will demonstrate how we utilize our innovative biomimetic platform for the temporal display of integrin-engaging cell-adhesive signals. Transient display of αVβ3-selective ligands instructed fibroblast cells to reversibly spread and contract in response to changes in ligand exposure over multiple cycles, exhibiting a universal kinetic response. Also, cells that were triggered to spread and contract repeatedly exhibited greater enrichment of integrins in focal adhesions versus cells cultured on persistent ligand-displaying surfaces. This dynamic platform will allow us to uncover the molecular code by which cells sense and respond to changes in their environment and will provide insights into ways to program cellular behavior. |
Tuesday, March 7, 2023 10:00AM - 10:12AM |
F11.00007: A multiscale whole-cell theory for cell migration under geometric confinement C. Nadir Kaplan, Wenya Shu Cells actively sense and respond to the mechanical and geometric properties of the extracellular matrix (ECM). To explain the experimental observations of the regulatory roles of the ECM mechanics and geometry in mesenchymal migration, we have developed a multiscale whole-cell theory that considers the sensing of the constricted ECM domains. Our theory quantitatively captures the experimental dependence of the cell shape and migration speed on ECM viscoelasticity and confinement geometry. Importantly, we find that the cell migration speed and the channel width are inversely proportional. Our results further indicate the effect of curved channel geometries on cell spreading, morphology, and migration speed. Altogether, our theory not only captures the mesenchymal migration dynamics under confinement but also provides experimentally testable predictions for cell migration in complex tissue microenvironments. |
Tuesday, March 7, 2023 10:12AM - 10:24AM |
F11.00008: Hyaluronan glycocalyx mechanically modulates cell shape and focal adhesion dynamics Yu Jing, Jessica Faubel, Katherine E Powell, Shlomi Cohen, Jennifer E Curtis Cells sense and adapt to the mechanical stimuli presented by their changing extracellular matrix microenvironment. Recent work has established that hyaluronan-rich glycocalyx generates sizable stresses that alter cell adhesion. Few if any studies have yet to elucidate the mechanoresponse of the cells experiencing these pericellular cues. Here we address that question using a tunable biomimetic glycocalyx to challenge adherent fibroblasts and to characterize their response. We demonstrate that the growth of biomimetic microns-thick hyaluronan glycocalyx at the cell-substrate impacts cell shape, cell adhesion, and focal adhesion dynamics. Given the range of biological processes that involve hyaluronan-rich glycocalyx, from synaptogenesis to cell migration to immune cell interactions, this work provides new insight into the impact on cells exposed to their own changing glycocalyx or that of others. |
Tuesday, March 7, 2023 10:24AM - 10:36AM |
F11.00009: Modelling cell trapping phenomenon and sub-diffusive cell migration on slow relaxing substrates Vivek Sharma, Ze Gong, Omkolade Adebowale, Ovijit Chaudhuri, Vivek b Shenoy Cell migration is an essential biological process that plays a key role in immune cell trafficking, embryogenesis, wound healing, and cancer metastasis. Biological tissues are compliant and exhibit viscoelasticity, showing stress relaxation in response to applied deformation. Substrate stress relaxation is emerging as a key mediator for diverse cellular processes such as cell proliferation, spreading, and stem cell differentiation. Cell migration on elastic substrates is frequently described as a purely diffusive, random walk. However, the impact of substrate stress relaxation on diffusive cell migration has not been studied. Here, by combining simulations and experiments, we systematically investigate the effect of substrate stress relaxation on cell migration phenotype. Using human HT1080 fibrosarcoma cells, our experiments found that faster substrate stress relaxation enhances the transition from sub-diffusive migration to super-diffusive migration. To understand the migration transition induced by stress relaxation, we have developed a cell migration model based on the motor clutch framework by introducing stochastic adhesion dynamics and membrane/cortex deformation. Our model shows, for the first time, that stochasticity (due to protein glassiness) in the binding dynamics of clutches causes cell trapping, leading to sub-diffusive migration on slow-relaxing substrates. Lastly, we have experimentally validated our model predictions by perturbating the system with different small molecule inhibitors (actin and myosin inhibitions) and analyzing their effects on migration phenotype. Thus, cell trapping and sub-diffusive migration governed by substrate stress relaxation facilitate new directions in cancer progression research. |
Tuesday, March 7, 2023 10:36AM - 10:48AM |
F11.00010: Probing Mechanical Interactions Between Lamellipodia and Surrounding Mechanical Environment June Hyung Kim, Taeyoon Kim Lamellipodia are sheet-like protrusion formed on the leading edge of cells and play a critical role in cell migration and mechanosensing of surrounding environments. Although the molecular players, architecture, and dynamics of the lamellipodia have been investigated extensively, it remains unclear how the lamellipodia mechanically interact with the underlying substrate via sparsely distributed focal adhesion points. To better understand the mechanical interaction between cells and their surrounding environment, we developed an agent-based model of a branched actin network consisting of F-actin, Arp2/3, actin cross-linking protein, myosin motor, and an underlying substrate. Using the model, we investigated the effect of various parameters on force development/relaxation, actin retrograde flow, substrate deformation, traction force, and focal adhesion dynamics. We found that lifetime of focal adhesion shows a biphasic dependence on its total area. Additionally, we identify the conditions for a steady state actin retrograde flow by imposing disassembly of F-actin in a myosin-induced contracting region and assembly near the leading edge. |
Tuesday, March 7, 2023 10:48AM - 11:00AM |
F11.00011: Model of how septin ring compartmentalization aids T-cell circumnavigation in extracellular matrices Sami Alawadhi, David M Rutkowski, Alexander Zhovmer, Erdem Tabdanov, Dimitrios Vavylonis In order to efficiently migrate through complex environments, T cells adopt a variety of migration modes including amoeboid and mesenchymal motions. Their ability to push the nucleus through narrow passages is critical for their migration through the extracellular matrix. Zhovmer et al. recently discovered that T cells in collagen matrices move with the aid of septin rings, which form around the nucleus at locations where extracellular matrix obstacles create high negative cell curvature. The resulting septin/F-actin rings subdivide the volume of the cell into separate compartments, with potentially different microenvironments. We developed a 2D computational model to test how such compartmentalization aids cell motility. In the model, beads representing the plasma membrane and nucleus move according to forces of bending rigidity, tension, contraction, fluctuating protrusions, and excluded volume interactions from encountered obstacles. Cell and nuclear volume conservation are implemented as area conservation forces. A weak nuclear centering force is implemented to represent cytoskeleton- and organelle-mediated nuclear centering. We assume that septin ring formation leads to compartment boundaries at sites where obstacles enforce proximity between the cell membrane and nucleus. We show that formation of these boundaries leads to a nuclear piston mechanism that enhances motility at high obstacle density. |
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