Mechanosignaling to the Cell Nucleus and Gene Regulation

Cells integrate physicochemical signals on the nanoscale from the local microenvironment, resulting in altered functional nuclear landscape and gene expression. These alterations regulate diverse biological processes including stem cell differentiation, establishing robust developmental genetic programs and cellular homeostatic control systems. The mechanisms by which these signals are integrated into the 3D spatiotemporal organization of the cell nucleus to elicit differential gene expression programs are poorly understood. In this review I analyze our current understanding of mechanosignal transduction mechanisms to the cell nucleus to induce differential gene regulation. A description of both physical and chemical coupling, resulting in a prestressed nuclear organization, is emphasized. I also highlight the importance of spatial dimension in chromosome assembly, as well as the temporal filtering and stochastic processes at gene promoters that may be important in understanding the biophysical design principles underlying mechanoregulation of gene transcription.