Multi-scale modeling of chemical-to-mechanical energy conversion in actin-based motility

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PROPOSAL NO.: 0505929PRINCIPAL INVESTIGATOR: A. LaddINSTITUTION NAME: University of FloridaMULTI-SCALE MODELING OF CHEMICAL-TO-MECHANICAL ENERGY CONVERSION IN ACTIN-BASED MOTILITYThis grant is to develop and validate a biologically relevant, multi-scale model of force generation by polymerization of the biopolymer, actin. Monomeric actin polymerizes into stiff filaments from surface-bound components, which crosslink and propel the surface forward. How the chemical energy involved in monomer addition is converted into mechanical work is critical in understanding cell motility, as well as for exploiting actin-based motility for micro-/nanoscale sensors and actuators. The extension of the wormlike model of the actin filaments to incorporate bending and torsion, as well as the incorporation of the hydration and gel will be studied. Intellectual merits include: incorporation of molecular-level kinetics and energetics into a mesoscale model of polymerizing and cross-linking filaments; the design of a computational framework for modeling the mechanical properties of solutions of stiff biopolymers such as actin, accounting for its resistance to bending and torsion, position and orientation-dependent chemical functionalization along the molecular backbone; and the coupling of the polymer dynamics to the surrounding solvent. Time-dependent variations in concentration of critical components of the polymerization process will also be studied. The broader impacts of the work include establishment of new collaborations between biochemists, physicists, and bioengineers studying actin networks, and chemical engineers developing numerical methods to simulate polymer solutions. New understanding of the coupling between filament elongation and force generation will be valuable in designing technological applications, such as microscale sensors and actuators using linear molecular motors based on actin motility. A small symposium will be organized to promote an objective discussion of the merits of various computational approaches to polymer simulations. The research will contribute to the education and training of graduate students in a collaborative, multidisciplinary environment and undergraduate students will participate in making specific calculations for software development and applications.