F-actin dynamics regulates collective cell migration by modulating cell shape and stress correlation

As an essential component in generating cell contractility, F-actin plays a pivotal role in collective cell migration. However, the mechanisms by which subcellular F-actin dynamics influence the collective behaviors of cell clusters across scales remain poorly understood. In this study, we developed a mechanical model to investigate how the dynamics of stress fibers and cryptic lamellipodia, prominent F-actin structures generating traction forces, regulate collective cell migration. Our results show that strengthening stress fibers significantly amplifies cell rearrangements and counteracts the high-density-induced inhibition of cell movements in the monolayer. It is attributed to the tension-caused cell elongation, which facilitates the growth of normalized mean-squared displacements in high-density cell monolayers. Moreover, the model shows that stronger stress fibers could effectively guide collaborative cell movements through enhancing the spatial correlation of maximum principal stress. Additionally, we found cryptic lamellipodia exhibit similar influence on collective cell migration. Our results bridge intracellular F-actin dynamics with collective cell migration, offering insights into the underlying mechanisms and their biological significance.