Oral: Mechanical Microenvironment Sensing and Cell Migration: Analysis of Motor-Clutch Dynamics

Understanding how cells sense the mechanical microenvironment and guide migration is a fundamental question in development, fibrosis and oncogenesis. This process has been previously elucidated by a motor-clutch model, that captures the oscillatory stick-slip dynamics observed experimentally, characterized by periodic changes in cell migration speed over time. Here, we systematically examine this model using both mean field theory and direct Monte Carlo simulation. Our analysis reveals two potential stable migration modes, which are not mutually exclusive: (1) non-slippery crawling, where the majority of integrins are linked to F-actin, resulting in a migration speed comparable to the speed of actin polymerization, and (2) slippery crawling, with only a small portion of integrins engaged, and a fast F-actin retrograde flow. The system's state—whether bistable, monostable, or exhibiting stick-slip behavior—is determined by substrate stiffness, friction, and the rate of actin polymerization, with boundaries between these regions shown analytically. Furthermore, deep within the stick-slip region, we show that the oscillatory behavior can be decomposed into two distinct processes: linear accumulation of traction forces and collective disengagement of integrins. Our theoretical results not only predict the migration modes of various cell types, but also forecast the oscillation period and the optimal substrate stiffness for maximum migration speed in the stick-slip regime.