Multiscale impact of nucleotides and cations on the conformational equilibrium, elasticity and rheology of actin filaments and crosslinked networks
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Kamm_Multiscale impact.pdf
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Author(s)
Bidone, Tamara Carla
Kim, Taeyoon
Deriu, Marco A.
Morbiducci, Umberto
Kamm, Roger Dale
Date Issued
February 2015
Journal
Biomechanics and Modeling in Mechanobiology
Publisher
Springer-Verlag
Citation
Bidone, Tamara Carla, Taeyoon Kim, Marco A. Deriu, Umberto Morbiducci, and Roger D. Kamm. “Multiscale Impact of Nucleotides and Cations on the Conformational Equilibrium, Elasticity and Rheology of Actin Filaments and Crosslinked Networks.” Biomech Model Mechanobiol (February 24, 2015).
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Author's final manuscript
Abstract
Cells are able to respond to mechanical forces and deformations. The actin cytoskeleton, a highly dynamic scaffolding structure, plays an important role in cell mechano-sensing. Thus, understanding rheological behaviors of the actin cytoskeleton is critical for delineating mechanical behaviors of cells. The actin cytoskeleton consists of interconnected actin filaments (F-actin) that form via self-assembly of actin monomers. It has been shown that molecular changes of the monomer subunits impact the rigidity of F-actin. However, it remains inconclusive whether or not the molecular changes can propagate to the network level and thus alter the rheological properties of actin networks. Here, we focus on how cation binding and nucleotide state tune the molecular conformation and rigidity of F-actin and a representative rheological behavior of actin networks, strain-stiffening. We employ a multiscale approach by combining established computational techniques: molecular dynamics, normal mode analysis and Brownian dynamics. Our findings indicate that different combinations of nucleotide (ATP, ADP or ADP-Pi) and cation (Mg[superscript 2+] or Ca[superscript 2+] at one or multiple sites) binding change the molecular conformation of F-actin by varying inter- and intra-strand interactions which bridge adjacent subunits between and within F-actin helical strands. This is reflected in the rigidity of actin filaments against bending and stretching. We found that differences in extension and bending rigidity of F-actin induced by cation binding to the low-, intermediate- and high-affinity sites vary the strain-stiffening response of actin networks crosslinked by rigid crosslinkers, such as scruin, whereas they minimally impact the strain-stiffening response when compliant crosslinkers, such as filamin A or α-actinin, are used.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.1007/s10237-015-0660-6
