NIH Center for Macromolecular Modeling & Bioinformatics University of Illinois at Urbana-Champaign

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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.