CAREER: Elucidating the material properties of complex tunable biopolymer networks using single-molecule nano stress-strain transducers and sensors

ID：MPS/DMR/BMAT（7623）1255446 主要研究者：安德森，雷伊ORG：圣地亚哥大学职业：使用单分子纳米应力应变传感器和传感器阐明复杂可调生物聚合物网络的材料特性智能优点：肌动蛋白是一种高度多功能的蛋白质，在众多肌动蛋白结合蛋白（ABP）的帮助下聚合并形成广泛的复杂网络。 这些网络，每个都是为特定的生物功能而设计的，具有非常不同的结构和动力学特性以及对应力和应变的机械响应。 肌动蛋白网络的层次性和可调性为自底向上设计多功能仿生材料提供了一条很有前途的途径。 然而，为了实现这样的设计，必须理解产生这种有吸引力的材料特性的分子动力学和相互作用。 大量的研究已经检查了肌动蛋白网络的粘弹性和机械响应，但这些研究无法揭示材料性质或材料内任何空间或时间变化的分子力学。 虽然单分子研究已经检查了单个肌动蛋白丝和肌动蛋白-ABP结构的机械性能，但仍然缺乏单个网络组件的力学和批量机械响应之间的联系。 使用荧光测力双光镊和一种新的技术，其中单分子作为纳米应力应变传感器和传感器，PI将首次，在分子水平上直接测量网络施加的阻力（皮牛顿精度）对分子级应变的响应（纳米/毫秒精度），同时实时成像和跟踪经历应变的单个分子。 这些测量-第一次-将揭示分子变形（应变）和阻力（应力）之间急需的联系，并将提供一个强大的描述之间的联系的各个网络组件的力学和散装机械响应。 因此，研究结果将填补长期以来在复杂生物聚合物网络力学行为方面的知识空白。更广泛的影响：该项目将为从分子和细胞生物学到材料科学和工程的一系列领域提供重要见解。 如果在分子水平上理解，生物聚合物网络中表现出的广泛的机械性能可以被利用来时空调节新型分层网络材料的机械性能。 开发和采用的创新技术也是高度通用的，可用于探测各种不同生物材料中存在的广泛的机械性能。 来自所有STEM学科的本科生已经并将继续在PI的研究中发挥核心作用。 PI还将继续指导当地高中学生，为所有学生创造丰富的跨学科研究经验。 为了进一步扩大PI研究的影响，她将在圣地亚哥大学开发一个高度跨学科的生物物理学专业课程，该课程将为本科生有效地为跨学科科学竞技场做出贡献并吸引更多女性进入物理科学领域。 PI将为该专业开发和教授三门新课程。 PI的研究和仪器将在每门课程中发挥不可或缺的作用。 PI，沿着与一群不同的STEM教师，也正在开发一个新的跨学科服务学习课程，其中本科生开发互动科学项目，他们与K-6学生在课后计划中执行，主要服务于第一代移民。 PI将开发一个暑期课程，其中完成本课程的生物物理学专业的学生将这些项目完善并传播到其他课外项目和机构。 研究结果，教学成果和推广模式将主要通过在同行评审期刊上发表，PI和学生在专业会议上的演讲以及通过强大的基于网络的方法进行传播。

ID: MPS/DMR/BMAT(7623) 1255446 PI: Anderson, Rae ORG: University of San DiegoTitle: CAREER: Elucidating the material properties of complex tunable biopolymer networks using single-molecule nano stress-strain transducers and sensorsINTELLECTUAL MERIT: Actin is a highly multifunctional protein that polymerizes and forms a wide range of complex networks with the help of numerous actin-binding proteins (ABPs). These networks, each designed for specific biological functions, have very different structural and dynamical properties as well as mechanical responses to stress and strain. The hierarchical nature and tunability of actin networks provides a promising route for the bottom-up design of multifunctional biomimetic materials. However, to implement such design, the molecular dynamics and interactions that give rise to such attractive material properties must be understood. Bulk studies have examined the viscoelasticity and mechanical response of actin networks, but such studies are unable to reveal the molecular mechanics underlying the material properties or any spatial or temporal variations within the material. While single-molecule studies have examined the mechanical properties of single actin filaments and actin-ABP constructs, a connection between the mechanics of single network components and the bulk mechanical response is still lacking. Using fluorescence force-measuring dual optical tweezers and a novel technique in which single molecules serve as nano stress-strain transducers and sensors, the PI will, for the first time, directly measure the resistive force exerted by a network at the molecular level (piconewton precision) in response to a molecular-scale strain (nanometer/millisecond precision) while simultaneously imaging and tracking single molecules experiencing the strain in real-time. These measurements -- the first of their kind -- will reveal the much-needed link between molecular deformation (strain) and resistive force (stress), and will provide a powerful description of the connection between the mechanics of the individual network components and the bulk mechanical response. Thus, results will fill a long-standing gap in knowledge regarding the mechanical behavior of complex biopolymer networks.BROADER IMPACTS: The project will provide critical insights to a range of fields from molecular and cellular biology to materials science and engineering. If understood at the molecular level, the broad range of mechanical properties exhibited in biopolymer networks could be harnessed to spatiotemporally regulate the mechanical properties of novel hierarchical network-based materials. The innovative techniques developed and employed are also highly versatile and can be used to probe a wide range of mechanical properties existing in a variety of different biomaterials. Undergraduates from all STEM disciplines have and will continue to play a central role in the PI's research. The PI will also continue to mentor local high school students, creating a rich interdisciplinary research experience for all students. To further broaden the impact of the PI's research, she will develop a highly interdisciplinary Biophysics Major program at the University of San Diego that will prepare undergraduates to contribute effectively to the interdisciplinary scientific arena and attract more women to the physical sciences. The PI will develop and teach three new courses for the major. The PI's research and instrumentation will play an integral role in each course. The PI, along with a diverse group of STEM faculty, is also developing a novel interdisciplinary service-learning course in which undergraduates develop interactive science projects that they execute with K-6 students in an afterschool program serving mainly first-generation immigrants. The PI will develop a summer program in which Biophysics majors who complete this course refine and disseminate these projects to other afterschool programs and institutions. Research results, pedagogical findings, and outreach models will be disseminated primarily via publication in peer-reviewed journals, presentations by the PI and students at professional conferences, and through robust web-based methods.