Original entry: Nefeli Georgoulia, APPHY 226, Spring 2009
Authors: L. Mahadevan & T.J. Mitchinson
Source: Nature, Vol. 435, 895-896, (2005)
Soft Matter key words: polymerization, strain, mechanical bending
This paper is a collaboration between microtubule guru T. Mitchison and biotheorist giant L. Mahadevan. The two join forces to explore past work and to offer novel interpretation to the ever-tantalizing question: How is the chemical energy from GTP hydrolysis harnessed to power growth and shrinkage of microtubules in dynamic instability? Microtubules are part of the cellular cytoskeleton and their structure is that of a hollow tube, formed by the the stacking of thirteen protofilaments. They form a dynamic network through the continuous polymerization and depolymerization of tubulin monomer. This dynamic behavior regulates cell compartmentalization, cellular cargo transportation and perhaps most notably the tearing apart of chromosomes during cell division. Thus, a lot of research is being directed towards understanding and creating a physical model that accounts for microtubule dynamics.
Soft Matter Snippet
From a soft matter perspective, microtubules have interesting polymerization traits. Unlike synthetic polymers, biopolymers have to expend energy -by hydrolyzing GTP- in order to assemble. Several models have been proposed to account for their dynamic behavior, and the authors list the following:
1) The thermodynamic-kinetic view. According to this one, GTP-bound tubulin binds on the polymerizing microtubule and it takes some time before GTP hydrolyses to GDP. This kinetic lag phase between hydrolisis and polymerization (i.e. the addition of a new GTP-tubulin monomer) accounts for the stabilization of microtubule ends. The GTP-tubulin at the growing microtubule tip is referred to as 'the GTP cap'. If concentration of free GTP-tubulin runs low in the cell, then the GTP cap is converted to GDP-bound tubulin faster than new monomers can attach, which results in detachment of monomers from the microtubule tip and shrinkage. (Figure 1, left).
2) The structural-mecahnical view. According to this later view once a microtubule becomes too long, the mechanical bending and strain of protofilament rings drives microtubule depolymerization. And whereas within the main microtubule, contact with neighbors forces protofilaments to be straight, at the ends protofilaments are free to curve backwards and form GDP-tubulin rings. These eventually break off and the microtubule shrinks until it reaches a new mechanically stable state. (Figure 1, middle)
3) The author's model. The authors launch into a molecular dynamics lattice simulation. They model the microtubule lattice as a bistable elastic sheet, whose energy landscape contains more than one equilibrium configuration. Curvature exchange provides the necessary energy for overcoming the energy barrier between states. (Figure 1, right).