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- W2914448462 abstract "The punctuated dynamics of cortical actomyosin are critical for cell migration in applications like cancer, wound healing, or morphogenesis, however the mechanical role and organization of cortical actomyosin is not well understood. We developed a Monte Carlo, particle-based computer simulation that resulted in emergent actomyosin asters. In particular, we were interested to understand the role of non-muscle myosin II's (motor) activation in emergent f-actin (filament) aster formation. Our model incorporates activation of individual motors through the transition from an inactive folded state to an active unfolded state, and the bundling of two active motors to form a processive motor capable of binding to filaments. In addition to considering how changing a single parameter affected the emergent filament asters, we introduced a spatial gradient of model parameters to mimic spatially controlled activation of motors, or filament polymerization. Recent studies have shown that regulation of motor activity is critical for directed fibroblast migration in response to a gradient of platelet derived growth factor, and we found that spatially inhibiting motor-filament binding resulted in spatial variations in filament aster formation. Additionally, motivated from studies with the small molecule ROCK inhibitor, Y-27632, and Calyculin A, which either disrupt or enhance the ability of non-muscle myosin II to exert force, and work from the Sellers lab on the biochemical properties of different types of co-assembled myosin isoforms, we simulated spatially controlled motor stiffness which directly affects the ability of motors to exert force to reorganize filaments. We found that not only was there a change in where asters emerged, but that we were able to generate a dynamic pulsatile aster structure where filament asters would dissipate and new asters would emerge. Results from our simulation will guide future experimentation for cortical actomyosin." @default.
- W2914448462 created "2019-02-21" @default.
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- W2914448462 date "2019-02-01" @default.
- W2914448462 modified "2023-09-26" @default.
- W2914448462 title "Simulating Emergent Spatiotemporal Actomyosin Dynamics to Understand Spatial Regulation of Non-Muscle Myosin II" @default.
- W2914448462 doi "https://doi.org/10.1016/j.bpj.2018.11.1372" @default.
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