Cell Response to Mechanical Microenvironment Cues Via Rho Signaling: From Mechanobiology to Mechanomedicine

Abstract

Mechanical cues in the cell microenvironment such as those from extracellular matrix propertoes, stretching, compression and shear stress, play a critical role in maintaining homeostasis. Upon sensing mechanical stimuli, cells can translate these external forces into intracellular biochemical signals to regulate their cellular behaviors, but the specific mechanisms of mechanotransduction at the molecular level remain elusive. As a subfamily of the Ras superfamily, Rho GTPases have been recognized as key intracellular mechanotransduction mediators that can trigger multiple cell activities such as proliferation, migration and differentiation as well as biological processes such as cytoskeletal dynamics, metabolism, and organ development. However, the upstream mechanosensors for Rho proteins and downstream effectors that respond to Rho signal activation have not been well illustrated. Moreover, Rho-mediated mechanical signals in previous studies are highly context-dependent. In this review, we systematically summarize the types of mechanical cues in the cell microenvironment and provide recent advances on the roles of the Rho signal in mechanotransduction in various cell activities, physiological processes, and diseases. Additionally, we overview the progress of mathematical models concerning Rho-regulated mechanochemical signal. Analysis of the mechanical roles of Rho GTPase partners would open a new paradigm of mechanomedicine for a variety of diseases.

Funding Information: This work on this topic is funded by the National Natural Science Foundation of China (No. 81872397).

Declaration of Interests: The authors declare no conflict of interest.

Keywords: Mechanotransduction, extracellular matrix properties, cell stretching, cell compression and shear stress, Rho GTPases, mechanomedicine