Review of Cellular Mechanotransduction

Abstract

Living cells and tissues experience physical forces and chemical stimuli in a human body. The process of converting mechanical forces into biochemical activities and gene expression is mechanochemical transduction or mechanotransduction. Significant advances have been made in understanding mechanotransduction at cellular and molecular levels over the last two decades. However, major challenges remain in elucidating how a living cell integrates signals from mechanotransduction with chemical signals to regulate gene expression and to generate coherent biological responses in living tissues in physiological conditions and diseases.

Figure 1. Long range mechanotransduction in the cytoplasm and the nucleus

A local shear stress of physiologic magnitudes and frequency is applied via integrins with a Arg-Gly-Asp tripeptide coated magnetic bead. The applied force concentrates at the stress fibers and propagates to long distances in the cytoplasm to directly activate enzyme Src [53] and Rac1 [54] and into the nucleus to stretch chromatin to upregulate transcription [73].

Figure 2. Soft melanoma tumor-repopulating cells extravasate efficiently to secondary sites of metastasis

The melanoma tumor-repopulating cells (TRCs) are injected into the pericardial cavity (to the left of the image, not shown) of a zebrafish. The undifferentiated soft TRCs arrest at the tail and squeezed out of the small blood vessel (green color) more efficiently than the differentiated stiff control melanoma cells. The efficient extravasation of the soft TRCs and the ensuing micrometastasis formation and metastatic colonization is inhibited by differentiating the TRCs with retinoic acid, stiffening F-actin with a polymerizing drug, or promoting F-actin via overexpressing small GTPase Cdc42 (from [93]).