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: Mechanical Forces Rule Cells and Their Molecules (Oct 2001)

Stretching FN-III-10

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Mechanical force is seen today as a key component of molecular processes in cells: forces can be signals as in touch receptors, products as in muscle action, and substrates as in the matrix surrounding moving cells . This view of molecular processes is the result of a series of ground-breaking investigations that have become possible only recently and is rapidly turning into a new field, mechanobiology (see recent review). A collaboration with V. Vogel and coworker (U. Washington, Seattle) has investigated structural changes accompanying stretch-induced unfolding events in type III fibronectin, a protein of the extracellular matrix, explaining the design of these proteins.

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  • Ultrastable cellulosome-adhesion complex tightens under load. Constantin Schoeler, Klara H. Malinowska, Rafael C. Bernardi, Lukas F. Milles, Markus A. Jobst, Ellis Durner, Wolfgang Ott, Daniel B. Fried, Edward A. Bayer, Klaus Schulten, Hermann E. Gaub, and Michael A. Nash. Nature Communications, 5:5635, 2014.
  • Mapping mechanical force propagation through biomolecular complexes. Constantin Schoeler, Rafael C. Bernardi, Klara H. Malinowska, Ellis Durner, Wolfgang Ott, Edward A. Bayer, Klaus Schulten, Michael A. Nash, and Hermann E. Gaub. Nano Letters, 15:7370-7376, 2015.
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    of the National Institutes
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