Deformations in Heterogeneous Biopolymer Networks

异质生物聚合物网络中的变形

• 批准号: 0804782
• 负责人: Jeffrey Urbach
• 金额: $ 42.51万
• 依托单位: Georgetown University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0804782&HistoricalAwards=false
• 关键词: Deformations; Heterogeneous; Biopolymer; Networks

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.

ID：MPS/DMR/BMAT(7623) 0804782 PI：Urbach，Jeffrey ORG：乔治城大学标题：异质生物聚合物网络中的变形智力优点：肌动蛋白、微管和中间丝等丝状蛋白的凝胶决定了大多数细胞的机械特性，并且它们的动态重排是迁移和分裂等关键细胞过程的基础。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蛋白和纤维蛋白等丝状蛋白网络决定的。这些网络具有一些共同特征：聚合物足够刚性，橡胶弹性理论无法很好地描述它们，聚合物本身仅占凝胶总体积的一小部分，并且它们的生物功能是由大量相关的介导的蛋白质。尽管它们很重要，但对于凝胶中的应力传播，还没有适合大多数生物聚合物网络的可靠的定量理论。该提案描述了一系列实验，旨在直接测量生物聚合物网络中细丝的运动及其对受控局部扰动的响应。生物聚合物和溶液的运动将被独立评估，目的是为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提供基础。测量结果将确定连续介质粘弹性准确描述网络变形场和解的位移的条件，并为连续介质理论扩展到异质响应体系提供基础。这些测量是通过 PI 实验室中运行的带有集成激光镊子的独特高速共焦显微镜实现的。这项工作最初将集中于肌动蛋白和胶原蛋白网络，其特性由不同的浓度、丝长度、丝刚性（通过丝束）以及交联剂和束剂类型和密度控制。在该项目的最后阶段，将研究微管（刚性）和肌动蛋白（半柔性）的混合网络，有或没有被动和主动（运动蛋白）连接。更广泛的影响：拟议活动的更广泛影响包括培训一支跨学科的队伍，并进一步将定量技术转化为生物研究人员。 该 PI 和联合 PI 最近发起了一个软物质研讨会系列，其中包括来自乔治城物理和化学系以及 NIH 和 NIST 的演讲者，并且很快将以此为基础扩大范围。在大学的支持下，他们发起了中大西洋软物质研讨会，首届活动于 2007 年 11 月 30 日在乔治敦举行。这个高度跨学科的研讨会吸引了来自中大西洋地区学术、工业和国家实验室的研究人员。 PI 还与墨西哥的 Tecnologico de Monterrey 建立了牢固的工作关系，涉及双向学生交流。 从事该项目的学生因此获得了远远超出大学范围的丰富的科学联系。 PI 是乔治城大学新的公共利益科学项目 (SPI) 的联合主任。 SPI 的构想是，乔治城大学在教育新一代公民科学家方面具有独特的优势，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运作和解决社会问题。该组织成立于 2005 年，目前年度预算超过 150,000 美元，PI 正在积极筹集资金，以扩大其活动以覆盖更多受众。提供两门研讨会课程：《塑造国家科学政策》和《科学与社会：重大挑战》，学生被安排在不同组织实习，包括核管理委员会、美国科学促进会科学、技术和安全政策中心以及国家科学院委员会关于全球健康。他们组织一年一度的国会访问日，为期一天的活动，包括立法制定过程的演示、科学政策讨论以及代表参与学生所在地区的各个办公室工作人员的访问。