9408905 Leibler The cytoskeleton is a polymer structure made out of protein fibers essential for intracellular transport, cell locomotion and division. This structure is dynamical and highly regulated through the cell cycle. Assembly and disassembly of the fibers and the action of associated motor proteins are out-of- equilibrium processes. The necessary free energy is provided by the hydrolysis of nucleotides (ATP, GTP) bound to the proteins. A Study will be initiated from a physics point of view - of the following aspects of this organization: o the dynamics of rigid and semiflexible protein fibers. The large persistence length of f-actin and microtubules allows direct visualization and study of their individual and collective behavior. o the non-equilibrium nature of the fiber assembly. It leads, for example, to a unique dynamic behavior of microtubules, called dynamic instability, in which the length fluctuations are of the order of the mean length. o the regulation of the fiber assembly. The dynamic instability, when regulated, is the basis of "trial and error", self-correcting architecture. Despite progress in the biochemistry if the assembly regulation, the spatio-temporal aspects (characteristic time and length scales) are poorly understood. o the transduction of chemical to mechanical energy. Both cytoskeleton fibers and associated motor proteins can be viewed as Brownian machines which are chemical-mechanical transducers. The understanding of these noisy machines must involve the methods of biochemistry and statistical mechanics. The approach is both experimental and theoretical. It involves physics and molecular biology departments, and the expertise of two industrial laboratories. Given the complexity of the problems involved, this multi-disciplinary approach seems necessary. ***
