title: Molecular investigations into the mechanics of actin in different nucleotide states.
abstract: Actin plays crucial roles in the mechanical response of cells to applied forces. For example, during cell adhesion, under the action of forces transmitted through integrins, actin filaments (F-actin) induce intracellular mechanical movements leading to changes in the cell shape. Muscle contraction results from the interaction of F-actin with the molecular motor myosin. Thus, understanding the origin of actin's mechanical flexibility is required to understand the basis of fundamental cellular processes. F-actin results from the polymerization of globular actin (G-actin), which contains one tightly bound nucleotide (ATP or ADP). Experiments revealed that G-actin is more flexible than F-actin, but no molecular-level understanding of this differential behavior exists. To probe the basis of the mechanical behavior of actin, we study the force response of G-actin bound with ATP (G-ATP) or ADP (G-ADP). We investigate the global unfolding of G-actin under forces applied at its ends and its mechanical resistance along the actin-actin and actin-myosin bonds in F-actin. Our study reveals that the nucleotide plays an important role in the global unfolding of actin, leading to multiple unfolding scenarios which emphasize the differences between the G-ATP and G-ADP states. Furthermore, our simulations show that G-ATP is more flexible than G-ADP and that the actin-myosin interaction surface responds faster to force than the actin-actin interaction surface. The deformation of G-actin under tension revealed in our simulations correlates very well with experimental data on G-actin domain flexibility.
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221, USA.
authors.forename: Ji Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Iverson
authors.forename: Ruxandra I
authors.initials: RI
authors.lastname: Dima
mesh_terms: D000199:Actins / Q000737:chemistry*; D000244:Adenosine Diphosphate / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry*; D009218:Myosins / Q000737:chemistry; D011485:Protein Binding; D058767:Protein Unfolding
chemical_list: D000199:Actins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009218:Myosins