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

建议没有。项目编号：0505929项目负责人：a . ladd机构名称：佛罗里达大学基于肌动蛋白的动力中化学能到机械能转换的多尺度模型该基金用于开发和验证生物聚合物肌动蛋白聚合产生力的生物学相关的多尺度模型。单体肌动蛋白从表面结合的组分聚合成硬丝，这些组分交联并推动表面向前。单体加成过程中所涉及的化学能如何转化为机械功，对于理解细胞运动，以及在微/纳米级传感器和致动器中利用肌动蛋白为基础的运动至关重要。将研究肌动蛋白丝的蠕虫状模型的扩展，以纳入弯曲和扭转，以及水化和凝胶的纳入。智力上的优点包括：将分子水平动力学和能量学纳入聚合和交联细丝的中尺度模型；设计了一个计算框架，用于模拟硬生物聚合物（如肌动蛋白）溶液的力学性能，考虑其对弯曲和扭转的抵抗力，以及沿分子骨架的位置和方向依赖的化学功能化；以及聚合物动力学与周围溶剂的耦合。聚合过程中关键组分浓度随时间的变化也将被研究。这项工作的广泛影响包括在研究肌动蛋白网络的生物化学家、物理学家和生物工程师之间建立新的合作关系，以及开发模拟聚合物溶液的数值方法的化学工程师。对纤维伸长和力产生之间耦合的新认识将在设计技术应用中具有价值，例如使用基于肌动蛋白运动的线性分子马达的微尺度传感器和致动器。将组织一次小型研讨会，以促进对各种计算方法在聚合物模拟中的优点的客观讨论。这项研究将有助于在合作、多学科的环境中教育和培训研究生，本科生将参与软件开发和应用的具体计算。

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.