Mechanosensing
Cells explore their environment by sensing and responding to mechanical forces. Many fundamental cellular processes, such as cell migration, differentiation, and homeostasis, take advantage of this sensing mechanism. At molecular level mechanosensing is mainly driven by mechanically active proteins. These proteins are able to sense and respond to forces by, e.g., undergoing conformational changes, exposing cryptic binding sites, or even by becoming more tightly bound to one another. In humans, defective responses to forces are known to cause a plethora of pathological conditions, including cardiac failure, pulmonary injury and are also linked to cancer. Microorganisms also take advantage of mechano-active proteins and proteins complexes. Employing single-molecule force spectroscopy with an atomic force microscope (AFM) and steered molecular dynamics (SMD) simulations we have investigated force propagation pathways through a mechanically active protein complexes.Spotlight: Life Under Tension (Jul 2006)
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The living state of biological cells manifests itself through mechanical motion on many length scales. Behind this motion are processes that generate and transform mechanical forces of various types. As with other cell functions, the machinery for cellular mechanics involves proteins. Their flexible structures can be deformed and restored, and are often essential for handling, transforming, and using mechanical force. For instance, proteins of muscle and the extracellular matrix exhibit salient elasticity upon stretching, mechanosensory proteins transduce weak mechanical stimuli into electrical signals, and so-called regulatory proteins force DNA into loops controlling, thereby, gene expression. In a recent review, the structure-function relationship of four protein complexes with well defined and representative mechanical functions has been described. The first protein system reviewed is titin, a protein that confers passive elasticity on muscle. The second system reviewed is the elastic extracellular matrix protein fibronectin and its cellular receptor integrin. The third protein system covered are the proteins cadherin and ankyrin involved in the transduction apparatus of mechanical senses and hearing. The last system surveyed is the lac repressor, a protein which regulates gene expression by looping DNA. In each case, molecular dynamics simulations using NAMD provided insights into the physical mechanisms underlying the associated mechanical functions of living cells. (more on our mechanobiology web site).
