Biomechanics of actin filaments: A computational multi-level study

• Published in: Journal of biomechanics Vol. 44; no. 4; pp. 630 - 636
• Main Authors: Deriu, Marco A, Bidone, Tamara C, Mastrangelo, Francesco, Di Benedetto, Giacomo, Soncini, Monica, Montevecchi, Franco M, Morbiducci, Umberto
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 24.02.2011; Elsevier; Elsevier Limited
• Subjects: Actin; Actin Cytoskeleton - chemistry; Actin Cytoskeleton - ultrastructure; Actins - chemistry; Actins - ultrastructure; Analytical, structural and metabolic biochemistry; Bending; Bending modulus; Biological and medical sciences; Biomechanics; Biomechanics. Biorheology; Biopolymer; Cell division; Coarse grain; Compressive Strength; Computation; Computer Simulation; Contractile proteins; Cytoskeleton; Elastic Modulus; Elastic network; Filaments; Flexibility; Fluctuations; Fundamental and applied biological sciences. Psychology; Holoproteins; Mechanical properties; Mechanics; Models, Chemical; Models, Molecular; Molecular dynamics; Monomers; Normal mode analysis; Persistence length; Physical Medicine and Rehabilitation; Protein Conformation; Proteins; Residues; Stiffness; Stress, Mechanical; Stretching; Studies; Tensile Strength; Tissues, organs and organisms biophysics; Topology; Torsion; Elastic modulus; Fluctuations; Elastic network; Normal mode analysis; Coarse grain; Molecular dynamics; Mechanical properties; Biomechanics; Actin; Biopolymer; Mechanics; Bending; Persistence length; Cytoskeleton; Stiffness; Torsion; Stretching; Computer simulation; Contractile protein; Biomedical engineering
• ISSN: 0021-9290; 1873-2380
• DOI: 10.1016/j.jbiomech.2010.11.014

Abstract The actin microfilament (F-actin) is a structural and functional component of the cell cytoskeleton. Notwithstanding the primary role it plays for the mechanics of the cell, the mechanical behaviour of F-actin is still not totally explored. In particular, the relationship between the mechanics of F-actin and its molecular architecture is not completely understood. In this study, the mechanical properties of F-actin were related to the molecular topology of its building monomers (G-actin) by employing a computational multi-level approach. F-actins with lengths up to 500 nm were modelled and characterized, using a combination of equilibrium molecular dynamics (MD) simulations and normal mode analysis (NMA). MD simulations were performed to analyze the molecular rearrangements of G-actin in physiological conditions; NMA was applied to compute the macroscopic properties of F-actin from its vibrational modes of motion. Results from this multi-level approach showed that bending stiffness, bending modulus and persistence length are independent from the length of F-actin. On the contrary, the orientations and motions of selected groups of residues of G-actin play a primary role in determining the filament flexibility. In conclusion, this study (i) demonstrated that a combined computational approach of MD and NMA allows to investigate the biomechanics of F-actin taking into account the molecular topology of the filament (i.e., the molecular conformations of G-actin) and (ii) that this can be done using only crystallographic G-actin, without the need of introducing experimental parameters nor of reducing the number of residues.