Box 1 | Cellular mechanotransduction

From the following article:

Mechanotransduction gone awry

Diana E. Jaalouk & Jan Lammerding

Nature Reviews Molecular Cell Biology 10, 63-73 (January 2009)

doi:10.1038/nrm2597

Several biological components, not mutually exclusive, have been proposed to act as cellular mechanosensors and are schematically depicted in a representative cell (see figure). Note that most of these features can be found in many cell types, although some (for example, changes in intercellular space) might only be relevant in a subset of cells. a | Stretch-activated ion channels in the plasma membrane open in response to membrane strain and allow the influx of calcium and other ions. b | In endothelial cells, the glycocalix, a layer of carbohydrate-rich proteins on the cell surface, can mediate mechanotransduction signalling in response to fluid shear stress. c,d | Cell–cell junctional receptors or extracellular matrix (ECM)–cell focal adhesions allow cells to probe their environments. e | Force-induced unfolding of ECM proteins, such as fibronectin, can initiate mechanotransduction signalling outside the cell. f | Intracellular strain can induce conformational changes in cytoskeletal elements such as filaments, crosslinkers or motor proteins, thereby changing binding affinities to specific molecules and activating signalling pathways. g | The nucleus itself has been proposed to act as a mechanosensor. Intracellular deformations can alter chromatin conformation and modulate access to transcription factors or transcriptional machinery. However, direct evidence for this mechanism is still lacking. h | Compression of the intercellular space can alter the effective concentration of autocrine and paracrine signalling molecules. Additionally, changes in G-protein-coupled receptors, lipid fluidity and even mitochondrial activity have been proposed as mechanosensors. Generally, almost all cells respond to mechanical stimulation with adaptive changes in cell function. These changes include short-term responses (such as increases (or decreases) in intracellular tension, adhesion, spreading or migration) as well as changes in long-term effects (such as in protein synthesis and secretion, structural reorganization, proliferation and viability). These effects are often mediated through multiple, overlapping and crosstalking signalling pathways.

Mechanotransduction gone awry