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: Protein and Membrane Mechanics (Sep 2003)

Tandem gate model in MscL

image size: 87.7KB

Living cells sense their environment and respond to its changes through proteins integrated into their outer membrane. These proteins mediate a broad range of cellular activities, including active and passive transport of materials across the membrane as well as response to osmotic shock, which can strain the cell membrane to the point of catastrophic bursting. Cells protect themselves through so-called mechanosensitive channels that open before the membrane tension grows too large. Molecular dynamics simulations and advanced analysis using NAMD and VMD have revealed in a recent report how the joint mechanics of membrane and protein opens a mechanosensitive channel called MscL. The finding promises to revolutionize the modern view of membrane - protein interaction: the membrane, far from being a homogeneous elastic sheet, exhibits a dramatic variation of tension across its thickness that proves to be decisive for the opening of MscL. More here.

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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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