Biomechanics of actin filaments: a computational multi-level study.
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.
Department of Mechanics, Politecnico di Torino, Italy. marco.deriu@polito.it
Marco A
MA
Deriu
Tamara C
TC
Bidone
Francesco
F
Mastrangelo
Giacomo
G
Di Benedetto
Monica
M
Soncini
Franco M
FM
Montevecchi
Umberto
U
Morbiducci
D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000648:ultrastructure*; D000199:Actins / Q000737:chemistry* / Q000648:ultrastructure*; D019245:Compressive Strength; D003198:Computer Simulation; D055119:Elastic Modulus; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D013314:Stress, Mechanical; D013718:Tensile Strength
D000199:Actins