A Computational Investigation of Asymmetric Emergent Structures in Actomyosin Dynamics During Chemotaxis

Abstract

We have developed a particle-based computer simulation to study emergent properties of the actomyosin cytoskeleton. In particular, our model accounts for biophysical interactions between filamentous actin (f-actin) and non-muscle myosin II (NM II). Our investigations were motivated by recent studies that demonstrate regulation of myosin activity is critical for directed migration of fibroblasts responding to gradients of platelet derived growth factor so we have incorporated the dynamics for NM II formation. Individual NM II transition from a folded inactive state to an active unfolded state. Once active, two NM II bundle together to create a processive NM II mini-filament capable of binding to f-actin. We performed a parametric analysis that led to the identification of biophysical parameters that control the formation of f-actin asters. We identified that aster formation was sensitive to filament length and the ability of motors to exert a spring-like force via changes in the spring constant for motors, or the maximum stretch allowed. When we considered the steps for NM II assembly, we found that inhibiting motor-filament binding and not motor activation or motor bundling was responsible for disrupting the actin morphology. Extending the bulk parameter analysis, we simulated chemotaxis by introducing the parameters to the computational simulation in a spatial gradient. We found that spatially regulating the ability of NM II to bind to f-actin resulted in a significant variation in actomyosin morphology in space. Additionally, we were able to generate a dynamic pulsatile aster structure through spatially regulating motor stiffness. Our identification of spatial regulators with the computational simulation will help guide future experimentation.