Bulletin of the American Physical Society
APS March Meeting 2022
Volume 67, Number 3
Monday–Friday, March 14–18, 2022; Chicago
Session G07: Physics of Cytoskeleton IIFocus Recordings Available
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Sponsoring Units: DBIO Chair: Arpita Upadhaya, University of Maryland, College Park Room: McCormick Place W-179A |
Tuesday, March 15, 2022 11:30AM - 12:06PM |
G07.00001: Active viscoelastic composites generate self-regulating asters with programmable lifetimes Invited Speaker: John P Berezney The out-of-equilibrium active reorganization of cytoskeletal networks by molecular motors is necessary for fundamental life processes, such as cell division, cell motility, and environmental sensing. While the passive structure and mechanics of such materials have been well documented, the effects of their steady-state out-of-equilibrium reorganization is a site of current research. In this work, we introduce an active cytoskeletal composite material whose viscoelasticity is controlled by the actin filament concentration. Three qualitatively different states are observed: (1) an extensile fluid phase, (2) localized aster-like contractile structures in coexistence with an extensile fluid, and (3) a bulk contractile gel. The aster-like state consists of locally contracted heterogeneous structures that maintain their complex layered structure over a range of sizes. While the actin concentration triggers a contractile state in coexistence with the active fluid, the resultant filament-rich structures are transient and their lifetimes increase with actin concentration. These results demonstrate that self-organized dynamical states and patterns, evocative of those observed in the cytoskeleton, do not require precise biochemical regulation but can arise due to purely mechanical interactions of actively driven filamentous materials |
Tuesday, March 15, 2022 12:06PM - 12:18PM |
G07.00002: Tuning cellular contractility by assembly of subcellular actomyosin structures Wen-hung Chou, Mehdi Molaei, Huini Wu, Jordan R Beach, Patrick W Oakes, Margaret Gardel Cells require mechanical forces to perform dynamic processes, such as cell migration. Mechanical output of the cell is tuned by the actomyosin cytoskeleton, where myosin motors pull on F-actin networks in cells to generate contractile forces. However, it is unclear how forces at the cellular scale can be regulated by the subcellular arrangement of actomyosin structures. To this end, we aim to quantitatively characterize how actomyosin assemblies remodel in cells leading to varying levels of contractility. Using quantitative microscopy, we observe that myosin appears as punctate structures in cells, suggesting that myosin locally accumulates in clusters. The number of myosin in these clusters shows a heavy-tailed distribution, with larger clusters located on thick F-actin bundles. In more contractile cells, for example by activating RhoA, both the number and the size of myosin clusters increase. This reflects an increase in the density of myosin motors at the subcellular scale, which correlates well with the measured mechanical energy density produced by the cell. With a simple simulation, we further show that the distribution of myosin clusters can be altered by the F-actin network. Our results can provide insight on how actomyosin assemblies tune cellular contractility. |
Tuesday, March 15, 2022 12:18PM - 12:30PM |
G07.00003: Force chains lead to long range percolation of forces produced by myosin motors in a disordered cytoskeleton network Abhinav Kumar, David A Quint, Kinjal Dasbiswas Myosin motors produce contractile forces in the actin cytoskeleton of animal cells and are responsible for cell shape changes and locomotion. Myosin generated forces percolate through a disordered elastic crosslinked actin network mediating mechanical interactions between distant myosin motors. Long-range Myosin-myosin interactions can produce energetically favorable ordered structures of myosin in the form of stacks, which are observed in non-muscle cells. We model myosin motors as force dipoles embedded in a random fiber network with linear elastic elements that have both bending and stretching moduli. This model captures the disordered nature of the cytoskeletal network and its nonlinear and anisotropic elastic properties. Minimizing the network elastic energy generated by two motors separated over a distance in the fiber network, we discovered favorable spatial configurations of myosin motors. These optimal configurations reveal force chains and strain clusters that show long range force transmission when compared to a corresponding linear elastic medium. Further, analyzing local network bond orientation can show preferential alignment of fibers. Finally, we predict how the mechanical interactions change with distance and orientation of myosin and network density. |
Tuesday, March 15, 2022 12:30PM - 12:42PM |
G07.00004: Mechanical coupling between the actomyosin and microtubule systems during T-cell activation Ivan A Rey Suarez, Arpita Upadhyaya Activation of T-cells leads to the formation of immune synapses (IS) with antigen-presenting cells. This requires T-cell polarization and coordination between the actomyosin and microtubule cytoskeletons. The interactions between these two cytoskeletal components during T-cell activation are not well understood. Here, we elucidate the interactions between microtubules and actin at the IS with high-resolution fluorescence microscopy. We show that microtubule growth dynamics is modulated by actin nucleators. Formin inhibition results in a moderate decrease in microtubule growth rates, which is amplified in the presence of integrin engagement. In contrast, Arp2/3 inhibition leads to an increase in microtubule growth rates. We also find that actin dynamics and actomyosin contractility play key roles in defining microtubule deformations and shape fluctuations. Interestingly, we find that nuclear mechanics modulates cytoskeletal dynamics and alters the coordination between actomyosin and microtubule cytoskeletons. Treatment with histone deacetylase inhibitor, trichostatin-A, causes nuclear softening, higher actin accumulation and disrupts centrosome polarization. Our results indicate a mechanical coupling between the actomyosin and microtubule systems during T-cell activation, that is essential for proper IS formation and maturation. |
Tuesday, March 15, 2022 12:42PM - 12:54PM |
G07.00005: Effects of disorder on the topological properties of microtubules Varsha Subramanyan, Saraswathi Vishveshwara, Smitha Vishveshwara Microtubules are macromolecular polymeric structures in eukaryotic cells that play key roles in intracellular transport, motility, and structure. It has been proposed that their physical structure allows for the existence of mechanical topological edge modes (Phys. Rev. Lett. 103, 248101). In this work, we employ a model to demonstrate that the charge distribution and lattice-like configuration of the microtubule additionally allow for electronic topological edge modes. We show this by modelling the microtubule as a cylindrical stack of Su–Schrieffer–Heeger chains forming an effective one-dimensional system. Further, we illustrate the robustness of these modes to low disorder strengths, as well as a topological phase transition that sets in at larger disorder strengths. We also discuss potential implications of disorder and topological defects for the phenomenon of dynamic instability in the microtubule as well as possible ways to model it within our system. |
Tuesday, March 15, 2022 12:54PM - 1:30PM |
G07.00006: Optimal control and design of cytoskeleton-based dynamic biomaterials Invited Speaker: Michael M Norton The ability of living systems to dynamically rearrange their constituents is one that we wish to endow in synthetic materials. While we have built active systems using reconstituted cytoskeletal components (such as microtubules, actin, motor proteins, and cross-linkers), there is no general framework for combining elements to achieve specific emergent spatiotemporal patterns. Using active nematics as an exemplar, I outline how the inverse problem toolset combined with a dynamical systems view of active matter enables both exogenous and endogenous material control. Inspired by new optogenetically enabled assays, I demonstrate how optimal control theory determines spatiotemporal light input that qualitatively changes the dynamics of an active nematic. Next, recognizing that the ultimate goal is to create autonomous materials, I present a framework for designing reaction-diffusion systems that couple to nematohydrodynamics to perform control endogenously. This framework uses a dynamical systems-centric machine learning technique to generate a set of partial differential equations that approximate the desired behavior. I end with a discussion about how the former, optimal control, might be applied to steer material flows in living systems. |
Tuesday, March 15, 2022 1:30PM - 1:42PM |
G07.00007: Characterizing cytoquakes, heavy-tailed fluctuations in the actomyosin cortex, using super-resolved micropost arrays Shankar N Sivarajan, Yu Shi, Katherine M Xiang, John C Crocker, Daniel H Reich The dynamics of the actomyosin network are responsible for a wide range of cellular behavior. The cellular cortex exhibits active fluctuations punctuated by rearrangements with large step-like displacements, termed “cytoquakes,” that show heavy-tailed distributions, and spatial and temporal correlations resembling those of earthquakes and avalanches [1]. Using high-resolution measurements of fluctuations in the cortex via arrays of flexible microposts, we find that the distributions of sizes of these cortical fluctuations are well-modeled by exponentially truncated Lévy distributions for multiple cell types and substrate stiffnesses. The tail exponent of these distributions, which governs their shape, exhibits a clear dependence on the time scale (lag time) of the measurements even when perturbations due to noise in the measurements are accounted for. The results suggest that cortical fluctuations over a wide range of time scales are the result of a single physical process, of which cytoquakes are the largest component. |
Tuesday, March 15, 2022 1:42PM - 1:54PM |
G07.00008: Roles of the Cytoskeletal Structure in Neurite Outgrowth Donghyun Yim, Kyle Miller, Daniel Suter, Taeyoon Kim Neurite outgrowth is a process in which neurons generate further projections, which is mainly driven by interactions between cytoskeletal components including microtubules, cross-linkers, and dynein motors. Previous studies suggested that dynein motors interact with and walk on a pair of neighboring microtubules transiently linked by cross-linkers. However, it remains elusive how these molecular interactions result in neurite elongation at a cellular scale. To investigate the mechanisms of neurite elongation, we constructed an agent-based model that consists of essential cytoskeletal elements with consideration of their mechanical properties and mechanical interactions. Our extensive parametric studies demonstrated that more microtubules are beneficial for accelerating the neurite outgrowth, whereas a higher number of crosslinkers are antagonistic for the neurite outgrowth. We also found how a change in the average length and bending stiffness of microtubules varies the neurite elongation rate. In addition, we showed how microtubule dynamics, i.e., growth, shrinkage, and fragmentation of microtubules, and the surrounding actin cortex affect neurite outgrowth. Our results provide important insights into understanding how neurite outgrowth emerges from molecular interactions. |
Tuesday, March 15, 2022 1:54PM - 2:06PM |
G07.00009: Dynamic behaviour of microtubules around the critical temperature and effect of the electric field produced by these vibrations on its environment NGANFO Y WILLY ANISET In this work, we study the microtubule as a ferroelectric system. The behaviour of microtubules around the critical temperature was evaluated and the effect of the electric field produced by the microtubules on its environment was determined. Also, the mean-field theory approximation (MFTA) was used to evaluate the total polarization and free energy around the critical temperature. These parameters are evaluated according to the physiological and critical temperatures in the absence and the presence of the electric field produced by the vibrations of the microtubule network. Results show that the microtubule (MT) has a spontaneous polarization in the absence of an electric field which collapses above the critical temperature. Moreover, the transition from ferroelectric to paraelectric state occurs with increasing physiological temperature. The microtubule stability is observed at the minimal free energy. The free energy is higher in the paraelectric state than in the ferroelectric state and changes its behaviour at high temperatures. The electric field stabilizes and orients the microtubule in the direction of the field. The microtubule produces electric fields that strongly interact with its biological environment at a short distance while long-distance interactions are weak. |
Tuesday, March 15, 2022 2:06PM - 2:18PM |
G07.00010: Organization and Dynamics of Crosslinked Actin Networks under Confinement Oghosa H Akenuwa, Steven M Abel The actin cytoskeleton is vital for intracellular transport in plant cells, where it remains challenging to understand how its organization is impacted by the interplay between physical confinement and the crosslinking of semiflexible actin filaments. We employ coarse-grained computer simulations to study the dynamics and organization of semiflexible actin filaments as we vary as the system shape, the number and type of crosslinking proteins, and the length of filaments. A variety of structures emerge, including isolated clusters of filaments, highly connected filament bundles, and networks of interconnected bundles with loops. We explore various measures of dynamics of network formation and find, with sufficiently large numbers of crosslinkers, a fast initial response followed by slower relaxation at longer times. Crosslinker properties impact the initial network response and subsequent relaxation. We characterize the bending energy of individual filaments and find, in some cases, highly unfavorable filament configurations that are difficult to relax. Finally, we examine organelle transport by molecular motors and the resulting impact on network organization. |
Tuesday, March 15, 2022 2:18PM - 2:30PM |
G07.00011: Regulation of F-actin size heterogeneity by formin and capping proteins Deb S Banerjee, Shiladitya Banerjee Actin filaments are one of the main components of the eukaryotic cytoskeleton that regulate cellular architecture and mechanical properties. While previous studies have mostly focused on the length control of individual actin filaments, it remains poorly understood how actin filaments in a cell regulate heterogeneity in size using a limited set of monomeric building blocks and actin binding proteins (ABP). Here we develop a theoretical model for the regulation of actin filament size heterogeneity by nucleation and growth rate modulation in a limiting pool of monomers and ABPs. We then investigate the roles of filament growth inhibition and promotion by capping and formin proteins on filament size heterogeneity. We find that heterogeneity can be increased by strong growth inhibition by capping and weak growth promotion by formin. A combination of both can give rise to bimodal size distribution and highly heterogeneous size distribution. Our study quantitatively predicts how heterogeneity in actin filament size can be regulated by tuning nucleation and growth rates. This emerging heterogeneity effects network morphology and distinct filament subpopulations may be crucial for building specialized actin structures (e.g., stress fiber) in a cell. |
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