Bulletin of the American Physical Society
APS March Meeting 2022
Volume 67, Number 3
Monday–Friday, March 14–18, 2022; Chicago
Session W07: Mechanobiology of Cell-Medium Interactions IIFocus Recordings Available
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Sponsoring Units: DBIO Chair: Wenya Shu Room: McCormick Place W-179A |
Thursday, March 17, 2022 3:00PM - 3:12PM |
W07.00001: Changes in biomechanical properties of neuronal cells measured by combined atomic force and fluorescence microscopy Cristian Staii We perform combined atomic force (AFM) and fluorescence microscopy measurements to determine how changes in the surrounding environment affect the biomechanical properties of neuronal cells at both the bulk (elastic modulus) and local (elasticity maps) levels. These high-resolution experiments allow us to distinguish between the contributions of the cellular membrane and of different cytoskeletal components to the cell elastic modulus. Our results demonstrate that the dominant mechanism by which the mechanical properties of the neuronal soma changes in response to external temperature is the contractile stiffening of the cytoskeleton induced by the change in myosin II activity. We find a power law relationship between cell elastic modulus and volume, and propose a simple model, based on elastic properties of biopolymer networks, that predicts the observed relationship. These results have significant implications for understanding neuronal functions, as ambient conditions such as external temperature or the stiffness of the growth substrate may change in physiological conditions, for example, under tissue compression or during neuronal growth, cell manipulation, and tissue regeneration. |
Thursday, March 17, 2022 3:12PM - 3:24PM |
W07.00002: Development of a 3D microfluidic platform for dynamic compression of tumor spheroids Young Joon Suh, Mrinal Pandey, Jeffrey E Segall, Mingming Wu Solid tumor stress caused by the rapid growth of tumor cells and abnormality of vascular vessels has long been associated with a poor prognosis of cancer. However, understanding of tumor mechanics has been limited largely to single cells under static compressive loads. In this study, we have developed a high-throughput microfluidic platform to study tumor spheroids under well-controlled dynamic compressive loads. The effect of compressive forces on invasion characteristics of a triple-negative malignant breast tumor spheroid (MDA-MB-231 cell line) was studied using the developed microfluidic platform. |
Thursday, March 17, 2022 3:24PM - 3:36PM |
W07.00003: Flow and forces on a rigid osteocyte immersed in bone: Effects of the flow network and pericellular matrix Jared Barber, Luoding Zhu, Hiroki Yokota, Sungsoo Na Osteocytes are cells that play an important role in bone remodeling. When exposed to forces, they emit signals that can cause other bone cells to produce or degrade the extracellular matrix that provides the bone with structure. The amount of force necessary to generate such signals in vitro has been observed to be at least tenfold more than the typical macroscale forces experienced by bones in everyday life. In vivo studies, however, can be difficult as cells are encased in a complex lacuna-canalicular network. In such networks, osteocytes are surrounded by fluid and small canals that link osteocytes together. How the geometry of such networks contribute to magnification of macroscale forces is not yet fully known. In addition, the presence of pericellular matrix, cell-associated proteins that occupy the fluid surrounding the cell, has also been theorized to have a potential role. In this study we use a two-dimensional model of a rigid osteocyte in a canalicular network to consider the questions of how the number of canaliculi and pericellular matrix may affect force generation on the osteocyte. The lattice Boltzmann equations (the D2Q9 model) are used to model the viscous incompressible flow. Differentiation of interpolated velocity and pressure fields is used to estimate the forces on the surface of the osteocyte. By developing the model using an idealized ellipsoidal geometry, the numerical and physiological capabilities are assessed. Initial results suggest that while a pericellular matrix tends to impede flow, it may enhance the fluid forces felt on the surface of the osteocyte. We will share these and more results, especially the effects of the number of canaliculi on force generation on the osteocyte. Such results carry implications for how to recover normal bone remodeling function in pathological scenarios such as osteoporosis. |
Thursday, March 17, 2022 3:36PM - 4:12PM |
W07.00004: Extracellular matrix viscoelasticity and its impact on cells Invited Speaker: Ovijit Chaudhuri The extracellular matrix (ECM) is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells in tissues. Over the last two decades, studies have revealed the important role that ECM elasticity plays in regulating a variety of biological processes in cells, including stem cell differentiation and cancer progression. However, tissues and ECMs are often viscoelastic, displaying stress relaxation over time in response to a deformation. Using hydrogels with tunable viscoelasticity for 3D cell culture, we have found that matrix viscoelasticity regulates the morphogenesis of pluripotent stem cells, cell migration, and cell division. |
Thursday, March 17, 2022 4:12PM - 4:24PM |
W07.00005: Probing Mechanical Interactions between Lamellipodia and Surrounding Mechanical Environments June Hyung Kim, Taeyoon Kim Lamellipodia are quasi-two-dimensional actin projection formed on the leading edge of the cell, playing an important role in sensing surrounding mechanical environments via focal adhesions. Although molecular players, architecture, and dynamics of the lamellipodia have been investigated extensively during recent decades, it still remains elusive how the lamellipodia mechanically interact with an underlying substrate via sparsely distributed focal adhesion points. To better understand the mechanical interactions, we developed an agent-based model of a branched actin network consisting of F-actin and Arp2/3 with myosin motors and an underlying substrate. Using the model, we demonstrated how each parameter affects force development/relaxation, actin retrograde flow, substrate deformation, traction force, and focal adhesion dynamics. We found that mechanical interactions between lamellipodia and the substrate are very different from those between finger-like projection called filopodia and the substrate, which have been probed actively by various modeling studies recently. We also identified conditions under which a dynamic steady state emerges for actin retrograde flow. |
Thursday, March 17, 2022 4:24PM - 4:36PM |
W07.00006: Cell spreading and migration on viscoelastic substrates: a bio-chemo-mechanical multiscale model Wenya Shu, C. Nadir Kaplan The extracellular matrix (ECM) is viscoelastic in nature. Recent evidence has shown that cells can sense both elasticity and viscous response of the ECM via focal adhesions. Although the sub-cellular level theories using the motor-clutch models revealed the critical role of the ECM viscoelasticity in focal adhesion dynamics, elucidating the cell mechanosensitive response demands a whole-cell model. To investigate the mechano-sensing of a mesenchymal cell on a viscoelastic substrate, we formulated a multiscale bio-chemo-mechanical model for the modeling of a whole cell. The proposed framework takes into account the feedback between the biochemical and biomechanical events and integrates the motor-clutch model at the sub-cellular scale with the cell structural analysis at the global level. Our model can quantitatively capture variations of the spreading area and migration speed in response to the ECM stiffness, in agreement with experiments. It further predicts the significant influence of the viscosity on cell spreading and migration on soft substrates. The intermediate substrate viscosity maximizes cell spreading while the maximum migration speed is achieved at high viscosity. These findings pave the way for designing biomaterials that optimize cell spreading and migration. |
Thursday, March 17, 2022 4:36PM - 4:48PM |
W07.00007: Hydraulics of cellular extension and contraction in Lacrymaria olor Samhita P Banavar, Eliott M Flaum, Manu Prakash Cells dynamically change shape and form to adapt to various functions. Amongst the fastest cellular movements are “neck” extensions of a unicellular protist, Lacrymaria olor, which changes its morphology in milliseconds in order to hunt for prey. These neck extensions are powered by motile cilia while the cortical helical cytoskeleton provides a structural architecture capable of supporting cellular extensions ranging from 10 to 20 body lengths in a few seconds. This unique transformation provides a framework for studying cellular hydraulics - flow of cytoplasmic content at rapid pace. Surprisingly, experimental measurements indicate that common organelles do not flow into the neck - implying a cytoplasmic phase separation between neck and body. Via theory and experiments, we demonstrate that a poroelastic cytoplasm enables these fast movements while protecting cellular architectures. Our current work provides a new approach for exploring extreme dynamical shape changes in eukaryotic cells. |
Thursday, March 17, 2022 4:48PM - 5:00PM |
W07.00008: Topological brakes in an ultrafast giant cell Ray Chang, Manu Prakash Understanding extremes in biology provides novel insights into the fundamental limits of life. To study cellular adaptations under extreme forces, we study the ultrafast contractions (50% body length contraction within 5-10 msec, peak acceleration 15g) in Spirostomum ambiguum, a giant single cell organism, as a model system. Utilizing TEM and confocal imaging, we discover a novel fenestrated cubic membrane architecture of rough endoplasmic reticulum (RER) wrapping around vacuolar meshwork, forming a 3D sheet spanning the entire cell. We explore the mechanical role of the entangled architecture to understand how giant cells dissipate energy in such a short time scale. We use a simple model with an overdamped molecular dynamics scheme where the RER-vacuolar meshwork is captured as hard particles entangled with inextensible strings, undergoing large deformation. Our simulations reveal that the topological confinement can induce jamming at a volume fraction significantly below critical value and dissipate more energy while preserving spatial relationship among vacuoles. Our findings suggest a new role of RER-vacuolar meshwork in a giant cell, which can be considered a metamaterial that applies topological brakes and preserves organelle architecture under extreme motility events. |
Thursday, March 17, 2022 5:00PM - 5:12PM |
W07.00009: Nanotopographic surfaces alter actin dynamics in primary rat astrocytes Kate M O'Neill, Emanuela Saracino, Tamara Posati, Roberto Zamboni, Valentina Benfenati, Wolfgang Losert Astrocytes, the non-neuronal cells of the brain, are morphologically and functionally diverse. Their functional roles range from maintaining brain homeostasis to modulating neuronal communication. Astrocytes also display morphological phenotypes ranging from pancake shaped (immature "polygonal" cells) to star shaped (mature "stellate" cells). In all cases, astrocytes' roles are facilitated by their regulation of ion and water molecule flux across their membranes, which requires dynamic reorganization of the cytoskeleton. Our previous work discovered that astrocytes use dynamic actin waves to sense chemophysical cues corresponding to realistic changes in the brain's microenvironment. Here we build off that work using biocompatible, nanotopographic surfaces as mechanical "triggers" to perturb astrocytic actin dynamics. We use live confocal microscopy to capture dynamics in cells transduced with actin-GFP and grown on either control or nanotopographic surfaces. Then we employ an optical flow algorithm to analyze changes in actin dynamics. We characterize astrocytes' responses to these mechanical cues and use micron-scale alterations in actin dynamics to understand the cellular-level response to changes in the extracellular microenvironment. |
Thursday, March 17, 2022 5:12PM - 5:24PM |
W07.00010: Deciphering Vimentin-Microtubule interactions in cell polarity Renita B Saldanha Vimentin intermediate filaments (IF) and the centrosome are a critical part of the cell cytoskeleton, a complex active network that directs many cellular functions. Recent studies have shown that centrosome positioning is critical for directional cell movement. On the other hand, loss of vimentin IF increases cell motility and directional persistence in microfluidic channels. These studies indicate both vimentin and centrosome are associated with directional cell migration but their interactions are widely unknown. Using wild-type and vimentin- null mice embryonic fibroblast (mEF), we found that vimentin null cells exhibit lower expression of the centrosome protein CEP215 compared to wild-type cells. Furthermore, nocodazole washout experiments show that loss of vimentin disrupts microtubule re-nucleation from the centrosome. Together, our result suggests that vimentin impacts microtubule nucleation from the centrosome, which has important implications for proper cytoskeletal organization and persistent motion of cells. |
Thursday, March 17, 2022 5:24PM - 5:36PM |
W07.00011: A mathematical model of chemotactic endothelial cell migration in a fibrin-based hydrogel extracellular matrix Josep Ferré Torres The formation of new vasculature from existing blood vessels, or angiogenesis, occurs as a multistep process driven by an extensive collection of pro- and anti-angiogenic factors. In this process, the extracellular matrix (ECM) plays a crucial role due to its structural function, the store of mediators, such as vascular endothelial growth factor (VEGF), and matrix-cell interactions. A standard approach to study angiogenesis is to explore the underlying cellular mechanisms focusing on endothelial cell (EC) motility regulated by chemotactic stimulus, ignoring mechanotactic stimuli. In cultured ECs, it is possible to easily analyze, separately, the concentration of growth factors, namely VEGF, and the structure of the culture substrate, mimicking ECM material. |
Thursday, March 17, 2022 5:36PM - 5:48PM |
W07.00012: Stick-slip model of cell crawling Pierre Sens Cell crawling is ubiquitous in many biological processes from development to cancer. It is inherently a problem of mechanics, in which forces actively generated by the cell through consumption of chemical energy are transmitted to the environment through transient adhesion to allow for cell translocation. Spreading and crawling cells display rich non-linear dynamics reminiscent of excitable systems. These include periodic phases of growth and retraction of cellular protrusion, travelling waves along the cell edges, and spontaneous cell polarisation and crawling. I will discuss a theoretical model combining the stochasticity of cell-substrate adhesion and linear cell visco-elastic mechanics, in which the force-sensitive unbinding of adhesion bonds leads to a stick-slip dynamics. The model that recapitulate many of the remarkable dynamical features of crawling cells and illustrates the fundamental role of mechanics in regulating cell motility. |
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