Collaborative Research: Mechanics and Microrheology of Biomimetic Materials

建议：0907212/0907470 PI名称：Levine，Alexander/Dennin，MichaelProposal标题：协作研究：仿生材料的力学和微观流变学研究所：加州大学洛杉矶分校/加州大学欧文分校该奖项由材料研究部的生物材料项目颁发，以支持加州大学洛杉矶分校和加州大学欧文分校的合作努力，该奖项旨在研究分子马达的非平衡动力学与丝状肌动蛋白(F-肌动蛋白)的弹性非线性之间的相互作用，并确定网络的集体力学性质，采用协调的实验/理论方法来应对每个挑战。活细胞的细胞骨架主要是由交联的F-肌动蛋白构成的，在活细胞中，F-肌动蛋白通常由肌球蛋白等分子马达拉伸。这种细丝网络的力学性质已被证明与这些分子马达的活动状态有复杂的依赖关系，并取决于单个细丝的力学、它们的网络结构和网络的非平衡稳态的组合。详细地了解这个网络的力学如何被它的内部应力状态(由内源分子马达施加)控制，将使我们能够更好地理解细胞如何控制它们的力学和形态，发展对细胞如何感知和对其周围施加力量的理解。到目前为止，这一领域的重点是将材料的平衡集体(非线性)响应性质与其成分的分子结构联系起来。有了这个奖项，与朗缪尔单分子膜的空气/水界面相关的F-肌动蛋白网络将被研究。然后，这些2D网络将被分子马达拉紧，并使用宏观和微观流变学进行研究，以阐明网络结构(通过对一些细丝进行荧光标记观察)和非平衡应力状态与其集体力学的潜在关系。网络的(准)二维性质允许直接观察局部网络结构和应变状态，并提供了一种快速原位化学修饰体系的方法。对这些生物聚合物网络的实验可以提供对生物聚合物网络的非平衡稳态的主动控制的洞察力，从而允许创建具有可逆可调机械性能的凝胶。了解这种典型的细胞骨架生物聚合物网络可能有助于开发具有可寻址机制的新型仿生活性材料。对研究生和本科生进行软材料生物物理学的实验和理论方面的教学和培训，以及开发一个解释微观流变学的网站是该奖项的其他部分。人类细胞被一个坚硬的生物聚合物网络所弥漫，这个网络的作用就像我们身体的骨骼一样，保持细胞的形状，并允许细胞通过作用于细胞骨架的分子马达的作用对环境施加压力。最近的进展使在实验室中解构然后重建细胞骨架的主要结构元素成为可能。利用这一奖项，测量了这种生物聚合物网络的机械性能，并将探索这些蛋白质细丝网络中网络结构、分子马达活性和大尺度力学之间的关系。这项工作的主要重要性是，这些研究将提供更好的理解，细胞如何使用分子马达对其环境施加力，以及这些马达的活动如何以可逆的方式改变网络的刚性。这一理解将有助于阐明基本的设计原则，人们可以根据这些原则来构建使用纳米机器(即分子马达)来主动控制其机械性能的人造活性材料。研究生和本科生都将接受与生物聚合物网络及其可逆可调机械性能相关的研究活动的培训。

Proposal:0907212/0907470 PI Name:Levine, Alexander/Dennin, MichaelProposal Title: Collaborative Research: Mechanics and Microrheology of Biomimetic Materials Institution: University of California-Los Angeles/University of California-IrvineThis award by the Biomaterials program in the Division of Materials Research in support of the collaborative efforts by University of California Los Angeles and University of California Irvine is to study the interaction between the nonequilibrium dynamics of molecular motors and the elastic nonlinearities of filamentous actin (F-actin) and determine the collective mechanical properties of the network, with coordinated experimental/theoretical approaches to address each of these challenges. The cytoskeleton of living cells is built primarily from cross-linked F-actin that, in living cells, is generically tensed by molecular motors such as myosin. The mechanical properties of this filament network have been shown to have a complex dependence on the state of activity of these molecular motors, and depend on a combination of the mechanics of the individual filaments, their network structure, and the non-equilibrium steady-state of the network. Understanding in detail how the mechanics of this network can be controlled by its internal stress state (imposed by the endogenous molecular motors) will enable us to better understand how cells control their mechanics and morphology, develop an understanding how cells sense and exert forces on their surroundings. To date, this field has focused on relating the equilibrium collective (non-)linear response properties of a material to the molecular structure of its constituents. With this award, F-actin networks associated with the air/water interface of a Langmuir monolayer will be studied. These 2D networks will then be tensed by molecular motors, and studied using both macro-and microrheology to elucidate the underlying relationship of network architecture (observed through fluorescent labeling of some of the filaments) and non-equilibrium stress state to its collective mechanics. The (quasi-) two-dimensional nature of the network allows for the direct observation of the local network structure, strain state, and provides a way to rapid in situ chemical modification of the system. Experiments on these biopolymer networks could provide insight about the active control of the nonequilibrium steady-state of biopolymer networks that allow the creation of a gel having reversibly tunable mechanical properties. Understanding this prototypical cytoskeletal biopolymer network may allow the development of novel biomimetic active materials with addressable mechanics. Teaching and training of graduate and undergraduate students in experimental and theoretical aspects of biophysics of soft materials, and developing a web site for the interpretation of microrheology are other parts of this award. Human cells are pervaded by a stiff biopolymer network that acts, much like the skeleton of our bodies, to maintain cellular shape and to allow the cell to exert forces on its environment through the action of molecular motors acting on this cytoskeleton. Recent advances have made it possible to deconstruct and then rebuild the principal structural elements of the cytoskeleton in the laboratory. With this award, the mechanical properties of this biopolymer network are measured, and will explore the relationship between network structure, molecular motor activity and large scale mechanics in these protein filament networks. The principal importance of this work is that these studies would provide better understanding how cells use molecular motors to exert forces on their environment and how the activity of these motors can modify the stiffness of the network in a reversible way. This understanding will help to elucidate fundamental design principles by which one may build artificial active materials that use nanomachines (i.e. molecular motors) to actively control their mechanical properties. Students, both graduate and undergraduate, will be trained in research activities that are related to biopolymer networks and their reversibly tunable mechanical properties.