Interplay between mechanics and signalling in regulating cell fate

Mechanical signalling affects multiple biological processes during development and in adult organisms, including cell fate transitions, cell migration, morphogenesis and immune responses. Here, we review recent insights into the mechanisms and functions of two main routes of mechanical signalling: outside-in mechanical signalling, such as mechanosensing of substrate properties or shear stresses; and mechanical signalling regulated by the physical properties of the cell surface itself. We discuss examples of how these two classes of mechanical signalling regulate stem cell function, as well as developmental processes in vivo. We also discuss how cell surface mechanics affects intracellular signalling and, in turn, how intracellular signalling controls cell surface mechanics, generating feedback into the regulation of mechanosensing. The cooperation between mechanosensing, intracellular signalling and cell surface mechanics has a profound impact on biological processes. We discuss here our understanding of how these three elements interact to regulate stem cell fate and development. Mechanical signalling underlies multiple, fundamental biological processes. Mechanical signals can originate from substrate physical properties or shear stresses, and from changes in the physical properties of the cell surface. The mechanisms underlying these two classes of outside-in signalling and their roles in the regulation of intracellular signalling in cell fate and development are becoming increasingly understood.