NANO- AND MICROMECHANICAL PROPERTIES OF HIERARCHICAL BIOLOGICAL MATERIALS Superelasticity, energy dissipation and strain hardening of vimentin coiled-coil intermediate filaments: atomistic and continuum studies

Vimentin coiled-coil alpha-helical dimers are elementary protein building blocks of intermediate filaments, an important component of the cell’s cytoskeleton that has been shown to control the large-deformation behavior of eukaryotic cells. Here we use a combination of atomistic simulation and continuum theory to model tensile and bending deformation of single alpha-helices as well as coiled-coil double helices of the 2B segment of the vimentin dimer. We find that vimentin dimers can be extended to tensile strains up to 100% at forces below 50 pN, until strain hardening sets in with rapidly rising forces, approaching 8 nN at 200% strain. We systematically explore the differences between single alpha-helical structures and coiled-coil superhelical structures. Based on atomistic simulation, we discover a transition in deformation mechanism under varying pulling rates, resulting in different strength criteria for the unfolding force. Based on an extension of Bell’s theory that describes the dependence of the mechanical unfolding force on the pulling rate, we develop a fully atomistically informed continuum model of the mechanical properties of vimentin coiled-coils that is capable of predicting its nanomechanical behavior over a wide range of deformation rates that include experimental conditions. This model enables us to describe the mechanics of cyclic stretching experiments, suggesting a hysteresis in the force–strain response, leading to energy dissipation as the protein undergoes repeated tensile loading. We find that the dissipated energy increases continuously with increasing pulling rate. Our atomistic and continuum results help to interpret experimental studies that have provided evidence for the significnificance of vimentin intermediate filaments for the largedeformation regime of eukaryotic cells. We conclude that vimentin dimers are superelastic, highly dissipative protein assemblies. Introduction: the structure of vimentin intermediate filaments and role in eukaryotic cells Together with beta sheets, alpha helical (AH) structures are the most abundant secondary structures found in proteins. These two patterns are particularly common because they result from hydrogen bonding between the N–H and C=O groups in the polypeptide backbone. An alpha helix is generated when a single polypeptide chain twists around on itself stabilized by hydrogen bonds (H-bond) made between every fourth residue, linking the O of peptide i to the N of peptide i + 4 in the residue chain. Consequently, at each convolution, three H-bonds are found in parallel arrangement that stabilize the helical configuration [1]. Another particularly stable configuration, found for the first time in keratin intermediate filaments (IFs) about 50 years ago, are alpha helical coiled-coils, where the primary structure reveals a pronounced seven residue periodicity (abcdefg)n, called a heptad repeat. Within this repeat, positions ‘‘a’’ and ‘‘d’’ are preferably occupied with nonpolar residues [2] such as LEU, ALA, VAL or ILE. The hydrophobic residues—consequently concentrated on one side—are the reason for the coiled-coil structure. In order to avoid contact with surrounding water molecules, AHs assemble into coiled-coils by wrapping T. Ackbarow M. J. Buehler (&) Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA e-mail: [email protected]