Bulletin of the American Physical Society
APS March Meeting 2020
Volume 65, Number 1
Monday–Friday, March 2–6, 2020; Denver, Colorado
Session X19: Frontiers in Actomyosin Stress Sensing and the Dynamics of the CytoskeletonInvited Prize/Award
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Sponsoring Units: DBIO Chair: John Crocker, University of Pennsylvania Room: 207 |
Friday, March 6, 2020 11:15AM - 11:51AM |
X19.00001: Elementary contractile unit and collective motor behavior Invited Speaker: Jacques Prost After introducing the main features characterizing an elementary contractile unit in cells as studied in M Sheetz lab in Singapore and Columbia New-York, I will recall theoretical results concerning motor collections obtained over the years. In particular I will show how a symmetry breaking transition, emergent feature of a large number of molecular motor collection, underpins a number of biological functions such as muscle oscillations. I will then show how a simple modification of the theoretical framework allows to understand all experimental observations including force build-up followed by a relaxation and the existence of half integer steps in the contraction/relaxation curve, which is a resurgence of a nanoscopic scale in a mesoscopic system. |
Friday, March 6, 2020 11:51AM - 12:27PM |
X19.00002: Cooperation, competition, and conviction in decision-making for motile cells Invited Speaker: Julie Theriot Efficient chemotaxis requires close coordination between the front and the rear of a migrating cell. For rapidly migrating neutrophils, persistent polarization is maintained by mutual antagonism between signaling networks active at the front versus those active at the rear. In addition, the structural organization of the actin cytoskeleton at the protruding front, dominated by a dendritically branched growing filament network, is dramatically different from the organization at the rear, dominated by myosin II contractility. Coordination between the front and the rear is mediated by mechanical feedback mechanisms, including cell-scale retrograde actin network flow, membrane tension, and dynamic myosin relocalization, that are optimized to balance migration persistence with turning efficiency. The generally stable state where individual migrating neutrophils maintain one front and one rear over many minutes can be disrupted when cells encounter obstacles that split the leading edge, causing the formation of multiple fronts. We have used microfluidic channels to establish a reproducible geometry for forcing cells to make a decision to convert one of two equally sized competing fronts into a retracting rear. The decision can be biased by optogenetic stimulation of the chemoattractant signaling pathway on one of the two competing fronts, but only during the latest stages of decision-making, indicating that both protruding fronts and retracting rears are generally unresponsive to changing stimuli unless mechanical competition has begun to “raise doubt”, rendering them amenable to reprogramming. |
Friday, March 6, 2020 12:27PM - 1:03PM |
X19.00003: Dissecting fat-tailed fluctuations in the cytoskeleton with active micropost arrays Invited Speaker: Daniel Reich The actomyosin cytoskeleton is critical to a wide range of cellular mechanobiology and mechanotransduction. However, the understanding of the connections between molecular-scale processes and cell-scale mechanical phenomena is not complete. Using active micropost array detectors containing magnetic actuators, we have characterized the mechanics and fluctuations of cells’ actomyosin cortex and stress fiber networks in detail. Both structures show consistent power law viscoelastic behavior and highly intermittent fluctuations with fat-tailed amplitude distributions. In the cortex, the dynamics are dominated by occasional large events, similar to what is seen in earthquakes or systems with avalanches. We have observed this behavior across multiple cell types and substrate stiffnesses, and the regular arrays of microposts enable measurement of the largest events’ symmetry and extent (up to several micrometers), revealing spatiotemporal dynamics resembling that seen in plastic solids. These results suggest that actomyosin components may self-organize into marginally stable plastic networks that give cells their unique biomechanical properties. |
Friday, March 6, 2020 1:03PM - 1:39PM |
X19.00004: How immune cells respond to physical cues – the role of cytoskeletal dynamics Invited Speaker: Arpita Upadhyaya The activation of lymphocytes, an essential step in the adaptive immune response, involves the binding of specialized receptors with antigens. This results in large-scale dynamics and re-structuring of the cytoskeleton, and movement of receptors into sub-micron clusters, which are critical for immune cell activation. Antigen presenting surfaces possess a wide variety of physical attributes, which influence cytoskeletal organization and receptor mobility, but how cells respond to these physical cues is not well understood. I will summarize our recent studies that examine how immune cells respond to physical cues such as surface mobility and topography. Regulation of membrane receptor mobility is important in tuning cellular response to external signals, such as during B cell signaling following the binding of B cell receptors (BCR) to antigen. We have used single molecule imaging to examine BCR movement and machine learning techniques to relate receptor trajectories to their signaling states. We find that the dynamic actin network fine-tunes receptor mobility and receptor-ligand interactions, thereby modulating B cell signaling. In vivo, B cells encounter surfaces of antigen presenting cells that are highly convoluted with a wide range of curvatures. We have used nanotopographic surfaces that allow systematic variation of geometric parameters to show that surface features on a subcellular scale influence B cell signaling and actin dynamics. Nanotopography-induced actin dynamics requires BCR signaling, actin polymerization, and myosin contractility. The topography of the stimulatory surface also modulates the distribution of BCR clusters and calcium signaling in activated B cells. Active cytoskeletal control of receptor diffusion may be a general feature that directs how diverse cell types respond to physical stimuli and transduce external signals into internal chemical signals. |
Friday, March 6, 2020 1:39PM - 2:15PM |
X19.00005: Cells in microgels: 3D printed microtissues and three-dimensional cell migration Invited Speaker: Tapomoy Bhattacharjee In most natural settings, cells thrive in 3D complex environments. The demand of studying cells in 3D has led to the development of many 3D growth media and various bio-printing techniques. Most 3D growth media use bio-degradable polymer networks; during 3D bio-printing cell-loaded polymeric filaments are spatially arranged that solidify during the printing process to preserve the shape. However, the spatial variation in network structure and the transience of degradable gels make quantitative cell behavior studies in these materials extremely challenging. Moreover, the general approaches of 3D bio-printing rely on intimate interactions between cells and specialized materials. Instead, we have developed a 3D growth medium from the jammed system of granular polyelectrolyte microgels that allows for 3D culture of cells. We find that single cell motility can be altered by varying inter-microgel pore spacing in 3D growth media. The self-healing nature of this growth media allows creation of highly precise tissue like structures by direct injection of cells inside the sacrificial 3D media. Finally, we have characterized the macroscopic rheological behaviors of this 3D medium and related them to the classic polyelectrolyte physics scaling laws that control single-microgel elasticity This work provides a revised approach of 3D cell culture and bio-printing and yields principles for predicting cellular migration and creating complex structures of cells with direct implications for tissue-engineering. |
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