Formation of perinuclear actin structures is driven by mechanosensitivity of actin polymerization

Abstract

Actin filaments are one of the most dynamic components of the cytoskeleton. Their fast polymerization, particularly in regions around the nucleus, allows the cell to react quickly and efficiently to external mechanical stimuli by controling nucleus morphology and position, thereby influencing the chromatin organization and gene transcription. While the biochemical mechanisms of actin polymerization are well known, the question why polymerization happens most prominently in the perinuclear region has so far remained elusive. Here, we develop a computational model for actin network formation whose key ingredients are: (i) a fully resolved orientational distribution of the local filaments, (ii) a strain-dependent depolymerization rate and (iii) active stress generation by actomyosin motors. With only these ingredients and without any ad-hoc assumptions on the spatial distribution of signaling molecules, our physics-based model explains the formation of perinuclear actin structures after mechanical stimulation as observed experimentally. In addition, our model also provides some insight into the role actin plays in positioning the nucleus, as it predicts the occurrence of a re-centering force when the cell nucleus is displaced, in quantitative agreement with experimental observations.