Moleculare machines push and pull cells in shape
Researchers from the FOM Institute AMOLF have discovered together with colleagues from the Vrije Universiteit how molecular machines work in unison to change the shape of biological cells.
Biological cells undergo drastic changes in shape when they migrate or divide. They rely for these shape changes on tiny molecular machines, which contract a skeleton of protein fibers inside the cell. It is a long-standing puzzle how the molecular machines actually coordinate to achieve directed contraction.
While each molecular motor by itself pushes on a protein fiber in one direction only, the cell contains a woven network of many fibers pointing in random directions. Thus the motors pull and push on the network in equal amounts. Marina Soares e Silva and her colleagues have been able to show that the random actions of the motors result in coordinated contraction, because the protein fibers respond differently to pushing than to pulling.
The network of protein fibers is essentially similar to a fishnet. The fibers strongly resist stretching by the motors, but they cannot support any compressive load since they will immediately buckle. This asymmetry leads to a coordinated contraction of the fiber network by the motors, even when the network starts out with a random configuration of fibers. This mechanical effect helps to explain how living cells use molecular motors to change their shape. An important step in the understanding of fundamental life processes like cell division and embryonic development.
Reference
'Active multistage coarsening of actin networks driven by myosin motors'
M. Soares e Silva, M. Depken, B. Stuhrmann, M. Korsten, F.C. MacKintosh, G.H. Koenderink,
PNAS, Published online before print May 18, 2011.
For more information please contact: Gijsje Koenderink
Figure 1. Phase 1. At the start of the self-organization process, the active actin networks are homogenous and the motor proteins are evenly distributed. Left panel: Fluorescence microscopy image of actin networks (in red) in the presence of myosin motors (green). (i) The network (red) and the motors (green) are initially randomly organized. (ii) A few minutes later, motors have formed small clusters (green). Scale bar (white) is 5 micrometers. Right panel: Cartoon diagram of phase 1: (i) the molecular motors (green) move with no preferred direction on the network (pink); (ii) myosin clusters coalesce. Inset: (i) Zoomed in view of the filaments of the actin network (polymers with a growing or plus end, in red) and myosin molecular motors (assemblies in green).
Figure 2. Phase 2. After 30 minutes the active actin networks become heterogeneous on a larger scale. Left panel: Fluorescence microscopy image of large myosin clusters (green) surrounded by a higher concentration of actin (bright red) than that of the surrounding network (darker red zones). Right panel: Cartoon diagram of phase 2: clusters of myosin (green) are too large to move through the network (pink) but they are able to actively capture actin filaments or network fragments (filaments in red). Actin filaments accumulate in shells around the myosin clusters (red rings around green circles).
Figure 3. Phase 3. After 45 minutes the actin-myosin clusters have merged into superstructures. Left panel: Fluorescence microscopy image showing large superstructures composed of several myosin clusters (green) that merged together and sandwiched the actin network in between them (red). Right panel: Cartoon diagram of phase 3: clusters of myosin (green) coalesce (black arrows) to form large superaggregates.