Durotaxis

Durotaxis is a form of cell migration in which cells are guided by rigidity gradients, which arise from differential structural properties of the extracellular matrix (ECM). Most normal cells migrate up rigidity gradients (in the direction of greater stiffness).

The process of durotaxis requires a cell to actively sense the environment, process the mechanical stimulus, and execute a response. Originally, this was believed to be an emergent metazoan property, as the phenomenon requires a complex sensory loop that is dependent on the communication of many different cells. However, as the wealth of relevant scientific literature grew in the late 1980s and throughout the 1990s, it became apparent that single cells possess the ability to do the same. The first observations of durotaxis in isolated cells were that mechanical stimuli could cause the initiation and elongation of axons in the sensory and brain neurons of chicks and induce motility in previously stationary fish epidermal keratocytes. ECM stiffness was also noted to influence cytoskeletal stiffness, fibronectin fibril assembly, the strength of integrin-cytoskeletal interactions, morphology and motility rate, all of which were known influence cell migration.

With information from the previous observations, Lo and colleagues formulated the hypothesis that individual cells can detect substrate stiffness by a process of active tactile exploration in which cells exert contractile forces and measure the resulting deformation in the substrate. Supported by their own experiments, this team coined the term "durotaxis" in their paper in the Biophysical Journal in the year 2000. More recent research supports the previous observations and the principle of durotaxis, with continued evidence for cell migration up rigidity gradients and stiffness-dependent morphological changes

The rigidity of the ECM is significantly different across cell types; for example, it ranges from the soft ECM of brain tissue to that of rigid bone or the stiff cell wall of plant cells. This difference in rigidity is a result of the qualitative and quantitative biochemical properties of the ECM or in other words, the concentration and categories of the various macromolecules that form the ECM meshwork. Though the ECM is composed of many intracellularly-synthesized components - including a number of glycosaminoglycans (GAGs) and fibrous proteins such as fibronectin, laminin, collagen, and elastin - it is the latter two fibers that are most influential in defining the mechanical properties of the ECM.

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