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: Snap Fastener on Biological Cells (Dec 2004)

Integrin-RGD binding under force

image size: 198.4KB
made with VMD

Biological cells must be capable of attaching themselves to their surroundings. For this purpose they utilize fibrillar proteins, such as fibronectins, that grasp cells through cell surface receptors integrins. The latter act as snap fasteners to the extra-cellular fibrils. The growth, movement, and survival of cells are all dependent on the ability of integrins to fasten cells upon intra-cellular signals or to signal inwards that something has become fastened on the cell surface. The major fastener on integrins are simple divalent ions like Mg++ or Ca++ that can adhere to specific molecules with amazing strength, even though the interaction at the cell surface is exposed to water. Computer simulations using NAMD, reported recently, revealed a dynamic picture of the interactions used by cells to link themselves to the extra-cellular matrix. They showed that it is actually a brave water molecule that is recruited by integrins as a protective shield for the interaction. The simulations provide for the first time a detailed view of how cell tissues are stabilized through surface ions against mechanical stress.

Related Spotlights

Related Publications
Related Research
Publications Database
  • 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.
  • Funded by a grant from
    the National Institute of
    General Medical Sciences
    of the National Institutes
    of Health