Hierarchical nanomechanics of vimentin alpha helical coiled-coil proteins
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0978-GG10-05
Hierarchical nanomechanics of vimentin alpha helical coiled-coil proteins Theodor Ackbarow and Markus J. Buehler Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139
ABSTRACT Coiled-coil alpha-helical dimers are the elementary building blocks of intermediate filaments (IFs), an important component of the cell’s cytoskeleton. Therefore, IFs play a leading role in the mechanical integrity of the cells. Here we use atomistic simulation to carry out tensile tests on coiled-coils as well as on single alpha-helices of the 2B segment of the vimentin dimer that has been shown to control the large-deformation behavior of cells. We compare the characteristic force-strain curves of both structures and suggest explanations for the differences on this fundamental level of hierarchical assembly. We further systematically explore the strain rate dependence of the mechanical properties of the vimentin coiled-coil protein. We develop a simple continuum model capable of reproducing the atomistic modeling results. The model enables us to extrapolate to much lower deformation rates approaching those used in experiment. INTRODUCTION
1A
L1
1B
L12 2A L2
2B
head rod tail Together with beta sheets, alpha helical (AH) structures are Figure 1: The ≈45 nm long dimers are the elementary building the most abundant secondary blocks of vimentin intermediate filaments. A dimer consists of a structures found in proteins. Two head, tail (in red) and an elongated rod domain which is divided four alpha-helical coiled coils (1A, 1B, 2A, 2B) connected AH structures can assemble into into through linkers L1, L12, L2 (also red) [7]. Molecular dynamics particularly stable coiled-coil simulations are performed on alpha-helices, placed in the 2B dimers when most of its nonpolar segment (yellow). amino-acid side chains are concentrated on one side, leading to two alpha-helices wrapping around each other [1]. Coiledcoils are also the building blocks of vimentin intermediate filament (IF) dimers (Figure 1). IFs, in addition to microtubules (MTs) and microfilaments (MFs) are one of the three major components of the cytoskeleton in eukaryotic cells [2]. The cytoskeleton determines the shape and the mechanical properties of the cell and is furthermore responsible for numerous additional functions such as cell motility or protein synthesis [2-4]. In contrast to MTs and MFs, which consist of globular proteins, the elementary building blocks of IFs are hierarchically assembled fibrous proteins (Figure 2) [5-7]. The elementary building blocks of IF proteins are dimers (Figure 1), composed of a head, a tail, and an extremely elongated central rod-domain, consisting of four coiled-coil alpha helices (1A, 1B, 2A, 2B) divided through linkers (L1, L12, L2) [6-8]. While the head and tail domain are greatly diverse for different IF-types, the individual length of alpha-helices, either ends of the rod as well as the position of the stutter (an irregularity in the heptad repeat in the 2B segm
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