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: Squeezing a Virus (Oct 2009)
Viruses are the simplest life forms known. In fact, one can question if they are life forms at all, as they cannot exist without infecting a host cell and using its machinery for replication. The virus is indeed just a package material surrounding a genetic message that instructs the host cell to replicate the virus. It looks like a soccer ball, but is a million times smaller (see also the March 2006 and January 2007 highlights). The infection, a well known example being infection of human cells by a flu virus, involves the virus to approach a human cell and dock onto it, become internalized by the cell, bursting then its package, called the capsid, and release the genetic message. The virus capsid needs to be sturdy and impermeable up to the approach to the cell, but then become brittle and porous to release the genetic material. Obviously, the virus capsid must have very distinct mechanical properties to function. To investigate these properties experimental and computational biophysicists teamed up. The experimentalists placed empty capsids of the hepatitis B virus onto a small chip and mechanically squeezed the capsid then with an extremely small tip, measuring how much force is needed to squeeze the spherical capsid down repeatedly. Computational researchers using NAMD repeated the experiment in simulation. As they reported recently, simulation gave the same forces as the experiment, but yielded also a detailed picture of the capsid mechanics. More on our "Molecular dynamics of viruses" web site.
