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：乔治敦大学异质生物聚合物网络中的变形智力优势：丝状蛋白质（如肌动蛋白、微管和中间丝）的凝胶决定了大多数细胞的机械性质，它们的动态重排是关键细胞过程（如迁移和分裂）的基础。类似地，在许多情况下，细胞外基质的机械和运输性质由丝状蛋白质如胶原蛋白和纤维蛋白的网络决定。这些网络具有一些共同的特征：聚合物足够刚性，以至于橡胶弹性理论无法很好地描述它们，聚合物本身占总凝胶体积的一小部分，并且它们的生物学功能由大量相关蛋白质介导。尽管它们的重要性，有没有可靠的定量理论，在凝胶中的应力传播，是适合于大多数生物聚合物网络。该提案描述了一系列旨在直接测量生物聚合物网络中细丝运动及其对受控局部扰动的响应的实验。生物聚合物和溶液的运动将被独立评估，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。测量将确定的条件下，网络的变形场和位移的解决方案准确地描述了连续粘弹性，并提供了基础的连续理论扩展到制度的非均匀响应。这些测量是通过一个独特的高速共焦显微镜与集成激光镊子，是在PI的实验室操作。这项工作最初将集中在肌动蛋白和胶原蛋白网络，通过不同的浓度，细丝长度，细丝刚度（通过细丝集束），交联剂和交联剂的类型和密度控制的属性。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，有无被动和主动（运动蛋白）连接。更广泛的影响：拟议活动的更广泛的影响包括培训跨学科的劳动力，并进一步将定量技术翻译给生物研究人员。 PI和co-PI最近发起了一个软物质研讨会系列，涉及来自乔治敦物理和化学系以及NIH和NIST的演讲者，并将很快从那里扩大。在大学的支持下，他们发起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届活动。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蒙特雷建立了强有力的工作关系，包括双向学生交流。 因此，从事该项目的学生可以获得丰富的科学联系，这些联系远远超出了他们大学的边界。 PI是新的乔治敦大学公共利益科学计划（SPI）的联合主任。SPI的构想认为，乔治敦在独特的定位，以教育新一代的公民科学家，能够弥合科学和公共政策之间的差距。SPI旨在让理科学生亲身接触政府的工作和解决社会问题。它成立于2005年，现在的年度预算超过150 000美元，公共信息机构积极参与筹款，以扩大其活动，接触更多的受众。提供两个研讨会课程，塑造国家科学政策和科学与社会：大挑战，学生被安置在不同的组织实习，包括核管理委员会，AAAS科学，技术和安全政策中心，以及国家科学院全球健康委员会。他们组织了一年一度的国会访问日，为期一天的活动分为关于创建立法，科学政策讨论的过程中的演示，并与代表参与学生的家庭地区的个别办公室的工作人员进行访问。