title: Mechanical response and conformational changes of alpha-actinin domains during unfolding: a molecular dynamics study.
abstract: Alpha-actinin is a cytoskeleton-binding protein involved in the assembly and regulation of the actin filaments. In this work molecular dynamics method was applied to investigate the mechanical behaviour of the human skeletal muscle alpha-actinin. Five configurations were unfolded at an elongation speed of 0.1 nm/ps in order to investigate the conformational changes occurring during the extension process. Moreover, a sensitivity analysis at different velocities was performed for one of the R2-R3 spectrin-like repeat configuration extracted in order to evaluate the effect of the pulling speed on the mechanical behaviour of the molecule. Two different behaviours were recognized with respect to the pulling speed. In particular, at speed higher than 0.025 nm/ps a continuous rearrangement without evident force peaks was obtained, on the contrary at lower speed evident peaks in the range 500-750 pN were detected. R3 repeat resulted more stable than R2 during mechanical unfolding, due to the lower hydrophobic surface available to the solvent. The characterization of the R2-R3 units can be useful for the development of cytoskeleton network models based on stiffness values obtained by analyses performed at the molecular level.
authors.affiliation: Department of Bioengineering, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133, Milan, Italy. monica.soncini@polimi.it
authors.forename: Monica
authors.initials: M
authors.lastname: Soncini
authors.forename: Simone
authors.initials: S
authors.lastname: Vesentini
authors.forename: Davide
authors.initials: D
authors.lastname: Ruffoni
authors.forename: Mario
authors.initials: M
authors.lastname: Orsi
authors.forename: Marco A
authors.initials: MA
authors.lastname: Deriu
authors.forename: Alberto
authors.initials: A
authors.lastname: Redaelli
mesh_terms: D000185:Actinin / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D001696:Biomechanical Phenomena; D003198:Computer Simulation; D019281:Dimerization; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012997:Solvents; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D012997:Solvents; D000185:Actinin