研究期間：10108~10207;A few topics related to the dynamics of the actin cytoskeleton in the in vivo and in vitro experiments will be studied by analytical theory and numerical simulation. First, a theoretical model will be studied to understand the role of actin network in the endocytosis of clathrin plaques. Clathrin plaques are clathrin-rich flat membrane domains in the ventral membrane of a cell adherent to an extracellular matrix. The endocytosis of these plaques has a distinct dynamics from the endocytosis of the usual clathrin pits because plaques remain flat even after they are engulfed by the cell. Based on experimental reports, we propose a theoretical model for the endocytosis of these plaques in which the polymerization and elasticity of the two-dimensional actin network around the plaque plays an important role. In our model, we assume that a plaque is a rigid disk due to the strengthening of the actin bundles on the clathrin lattice, a two-dimensional actin network adherent to the cell membrane grows from the rim of the plaque because of the assistance of protein cortactin. As the actin network grows, an inward contractile tension builds up until the ventral membrane buckles, pushes the membrane plaques into the cell. Careful numerical analysis will provide quantitative predictions that can be compared to experimental observations. To gain deeper understanding on the mechanical and dynamical properties of actin filaments, we also propose a bottom-up (although coarse-grained) approach to study the polymerization dynamics of actin filaments. In this model, the nucleotide-state-dependent elastic properties of the actin monomers will be taken into account, and the interplay of such peculiar elastic property with the ATP hydrolysis and the polymerization/depolymerization kinetics will be examined by both analytical theory and molecular dynamics simulation. The analysis will begin with a single actin filament under an external force. This study shall give us a phase diagram for stalled, buckled, and growth behavior of a single actin filament under external force. The role of thermal and chemical randomness will also be studied. Then we will study many parallel actin filaments under shared external force. In this study, the distribution of growing, stalled, and buckled filaments will be studied and we expect that rich actin dynamic behaviors will be revealed by systematic numerical analysis.
