Molecular Mechanics of the Filamin's Rod Domain

¹ University of California, Berkeley
² University of California Berkeley

^* To whom correspondence should be addressed. E-mail: mofrad{at}berkeley.edu.

Submitted on July 31, 2007
Revised on September 8, 2007
Accepted on 20 September 2007

	Abstract

Rearrangement of the actin cytoskeleton is integral to cell shape and function. Actin-binding proteins, e.g. filamin, can naturally contribute to the mechanics and function of the actin cytoskeleton. The molecular and mechanical bases for filamin's function in actin cytoskeletal reorganization are examined here using constant force pulling simulations. Simulations are performed by applying forces ranging from 25pN to 125pN for 2.5ns to the rod domain of filamin. Applying small loads (~25pN) to filamin's rod domain supplies sufficient energy to alter the conformation of the N-terminal regions of the rod. These forces break local hydrogen bond coordination often enough to allow side chains to find new coordination partners, in turn leading to drastic changes in the conformation of filamin, for example increasing the hydrophobic character of the N- terminal rod region, and alternatively activating the C-terminal region to become increasingly stiff. These changes in conformation can lead to changes in the affinity of filamin for its binding partners. Therefore, filamin can function to transduce mechanical signals as well as preserve topology of the actin cytoskeleton, all through the rod domain.

Key Words: actin-binding protein, cytoskeleton, filamin, mechanotransduction, molecular dynamics