A Two-Step Nuclear Mechanotransduction Model

Abstract

For cells to adapt to different tissues and changes in tissue mechanics, they must be able to respond to mechanical cues by changing gene expression patterns. These responses potentially involve major changes in nuclear organization and structure to reflect epigenetic changes in the nucleus. However, it is unclear how physical cues received at the plasma membrane integrate to the functional architecture of the cell nucleus. Recent evidence suggests that the nucleus responds to force via concurrent biochemical and mechanical pathways. Applying force to the plasma membrane of cells resulted in mechanical deformation of the nucleus and displacement of heterochromatin regions. Simultaneously, the actin cytoskeleton reorganized in response to force application, which further induced the translocation of transcription co-factor MKL from the cytoplasm to the nucleus. We present a minimal quantitative model incorporating active stresses and chemical kinetics to evaluate the reaction and timescales of nuclear reaction to force. Our work shows a minimal system of biochemical and mechanical effects working in tandem to recapitulate the observed effects of nuclear mechanosignaling.