Modelling Actin-MT Crosstalk in Migrating Cells

Abstract

Actin-Microtubule crosstalk regulates the polarity and morphology of migrating cells and encompasses mechanical interactions, mediated by crosslinkers, molecular motors, and cytoskeletal regulators. Recent experiments indicate that local microtubule depolymerization promotes local actomyosin retraction, whereas local microtubule polymerization promotes local actin-polymerization. Based on these observations, we develop a computational whole-cell model involving dynamic microtubules interacting mechanically and chemically with an active cell boundary. Specifically, the tips of microtubules send signals for local expansion or contraction to the active cell boundary, depending on whether they are in the growth or shrink phase. A rich, self-organized, dynamic behavior emerges, characterized by the repositioning of the microtubule-organizing center relative to the nucleus and the direction of migration. This also includes a variety of migration patterns, cell morphologies, and complex responses to obstacles in microfluidic and obstacle park environments. We demonstrate that microtubule length and cell boundary stiffness have a significant impact on these features, highlighting the need for new experimental investigations. Thus, the model provides a unified framework that explains a wide range of experimental observations and setups where actin-microtubule crosstalk plays a crucial role.