Deformations in Heterogeneous Biopolymer Networks

ID：MPS/DMR/BMAT(7623)0804782 PI：Urbach，Jeffrey ORG：乔治城大学题目：异质生物聚合物网络中的变形INTELLECTUCTUAL优点：丝状蛋白质的凝胶，如肌动蛋白、微管和中间丝决定大多数细胞的机械性能，它们的动态重排决定着关键的细胞过程，如迁移和分裂。同样，在许多情况下，细胞外基质的机械和运输特性是由胶原和纤维蛋白等丝状蛋白质网络决定的。这些网络有几个共同的特征：聚合物足够刚性，不能很好地用橡胶弹性理论来描述，聚合物本身只占总凝胶体积的一小部分，它们的生物学功能是由大量相关蛋白质介导的。尽管它们很重要，但目前还没有适用于大多数生物聚合物网络的可靠的定量理论来描述凝胶中的应力传播。这项建议描述了一系列实验，旨在直接测量生物聚合物网络中细丝的运动及其对受控的局部扰动的响应。将独立评估生物聚合物的运动和溶液，目的是提供一个基础，在此基础上开发和测试生物聚合物网络中的应力传递和材料传输模型。这些测量将确定用连续介质粘弹性精确描述网络变形场和溶液位移的条件，并为将连续介质理论扩展到非均匀响应区域提供基础。这些测量是由一台独特的高速共聚焦显微镜和集成的激光镊子实现的，该显微镜在PI的实验室中运行。这项工作最初将集中在肌动蛋白和胶原蛋白网络上，其特性由不同的浓度、长丝长度、长丝刚性(通过长丝束)以及交联剂和结束器的类型和密度来控制。在项目的最后阶段，将研究微管(刚性)和肌动蛋白(半柔性)的混合网络，有无被动和主动(马达蛋白)连接。BROADER影响：拟议活动的更广泛影响包括培训跨学科的劳动力和进一步将定量技术转化为生物研究人员。国际和平研究所和共同国际和平研究所最近发起了一个软物质研讨会系列，来自乔治敦大学物理系和化学系以及NIH和NIST的演讲者参加了研讨会，并将很快扩大范围。在大学的支持下，他们启动了中大西洋软物质研讨会，并于2007年11月30日在乔治敦举行了首场活动。这一高度跨学科的研讨会吸引了来自大西洋中部地区学术、工业和国家实验室的研究人员。国际和平协会还与墨西哥蒙特雷技术学院建立了牢固的工作关系，其中包括双向的学生交流。因此，从事这一项目的学生可以获得丰富的科学联系，远远超出他们所在大学的范围。PI是新的乔治敦大学公共利益科学项目(SPI)的联合主任。SPI的构想是，乔治敦大学在培养新一代公民科学家方面具有得天独厚的优势，能够弥合科学与公共政策之间的差距。SPI旨在让理科学生亲身接触政府的运作和社会问题的解决。它成立于2005年，现在每年的预算超过15万美元，国际和平协会正在积极开展筹款活动，以扩大其活动，以接触到更多的受众。开设了两门研讨会课程：塑造国家科学政策和科学与社会：重大挑战，学生们被安排在不同组织实习，包括核管理委员会、美国科学、技术和安全政策中心以及美国国家科学院全球健康委员会。他们组织一年一度的国会访问日，为期一天的活动包括介绍立法过程、科学政策讨论，以及与代表参与学生所在地区的个别办公室的工作人员进行访问。

ID: MPS/DMR/BMAT(7623) 0804782 PI: Urbach, Jeffrey ORG: Georgetown UniversityTitle: Deformations in Heterogeneous Biopolymer NetworksINTELLECTUAL MERIT: Gels of filamentous proteins such as actin, microtubules, and intermediate filaments determine the mechanical properties of most cells, and their dynamic rearrangement underlies critical cell processes such as migration and division. Similarly, the mechanical and transport properties of the extracellular matrix are, in many contexts, determined by networks of filamentous proteins such as collagen and fibrin. These networks share a few common features: The polymers are sufficiently rigid that they are not well described by rubber elasticity theory, the polymers themselves make up a small fraction of the total gel volume, and their biological functions are mediated by a vast array of associated proteins. Despite their importance, there is no reliable quantitative theory for the propagation of stresses in gels that is appropriate for most biopolymer networks. This proposal describes a series of experiments designed to directly measure the motion of filaments in biopolymer networks and their response to controlled, localized perturbations. The motion of the biopolymers and the solution will be independently assessed, with the goal of providing a basis on which to develop and test models of stress transmission and material transport in biopolymer networks. The measurements will determine the conditions under which the deformation field of the network and the displacements of the solution are accurately described by continuum viscoelasticity, and provide the basis for extensions of continuum theory into regimes of heterogeneous response. These measurements are made possible by a unique high-speed confocal microscope with integrated laser tweezer that is operational in the lab of the PI. The work will focus initially on actin and collagen networks, with properties controlled by varying concentration, filament length, filament rigidity (through filament bundling), and cross-linker and bundler type and density. In the last phase of the project, mixed networks of microtubles (rigid) and actin (semi-flexible) will be investigated, with and without passive and active (motor protein) linkages.BROADER IMPACTS: The broader impacts of the proposed activity include training an interdisciplinary workforce and furthering the translation of quantitative techniques to biological researchers. The PI and co-PI have recently initiated a Soft Matter Seminar Series that involves speakers from Georgetown Physics and Chemistry Departments, as well as from NIH and NIST, and will soon broaden from there. With University support, they have launched the Mid-Atlantic Soft Matter Workshop, with the inaugural event held at Georgetown on November 30, 2007. This highly interdisciplinary workshop drew upon researchers from academic, industrial, and national laboratories in the Mid-Atlantic Region. The PI has also established a strong working relationship with Tecnologico de Monterrey in Mexico which involves student exchanges in both directions. Students working on this project are thereby afforded a wealth of scientific contacts extending well beyond the borders of their university. The PI is the co-director of the new Georgetown University Program on Science in the Public Interest (SPI). SPI was conceived with the view that Georgetown in uniquely positioned to educate a new generation of citizen scientists, capable of bridging the gap between science and public policy. SPI is designed to give science students hands-on exposure to the workings of the Government and to societal problem-solving. Formed in 2005, it now has an annual budget of over $150,000, and the PI is actively engaged in fundraising to expand its activities to reach a larger audience. Two seminar courses are offered, Shaping National Science Policy and Science and Society: Grand Challenges, and students are placed in internships in diverse organizations including the Nuclear Regulatory Commission, the AAAS Center for Science, Technology, and Security Policy, and the National Academies Board on Global Health. They organize an annual Congressional Visit Day, a day-long event divided between presentations on the process of creating legislation, science policy discussions, and visits with staff from individual offices representing the home districts of the participating student.