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 PI：Anderson，RAE ORG：圣迭戈大学标题：Career：阐明使用单分子纳米应力-应变传感器和传感器的复杂可调生物聚合物网络的材料特性INTELLECTUCTUAL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(ABPs)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多功能仿生材料的自下而上设计提供了一条很有前途的途径。然而，要实现这种设计，必须了解产生如此吸引人的材料特性的分子动力学和相互作用。大量研究考察了肌动蛋白网络的粘弹性和力学响应，但这些研究无法揭示材料性质背后的分子力学或材料内部的任何空间或时间变化。虽然单分子研究已经检测了单个肌动蛋白细丝和肌动蛋白-ABP结构的力学性质，但单个网络组件的力学性能和整体机械响应之间的联系仍然缺乏。利用荧光力测量双光钳和单分子作为纳米应力-应变传感器和传感器的新技术，PI将首次在分子水平(皮牛顿精度)直接测量网络对分子尺度应变(纳米/毫秒精度)施加的阻力，同时实时成像和跟踪经历应变的单个分子。这些测量--这是此类测量中的第一次--将揭示分子变形(应变)和阻力(应力)之间亟需的联系，并将有力地描述单个网络组件的机械结构和整体机械响应之间的联系。因此，这些结果将填补关于复杂生物聚合物网络力学行为的长期知识空白。BROADER影响：该项目将为从分子和细胞生物学到材料科学和工程等一系列领域提供关键的见解。如果在分子水平上了解，生物聚合物网络中表现出的广泛的力学性质可以被利用来在时空上调节新型分级网络材料的力学性质。开发和使用的创新技术也具有很高的通用性，可以用来探索各种不同生物材料中存在的各种机械性能。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生，为所有学生创造丰富的跨学科研究体验。为了进一步扩大PI的研究影响，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项目，该项目将培养本科生有效地为跨学科科学舞台做出贡献，并吸引更多女性进入物理科学。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还与STEM教职员工一起开发了一门新的跨学科服务学习课程，在该课程中，本科生开发互动科学项目，他们与K-6学生在一个主要服务于第一代移民的课外项目中执行这些项目。PI将制定一个暑期计划，在这个计划中，完成这门课程的生物物理学专业的学生将改进这些项目，并将这些项目传播到其他课外项目和机构。研究成果、教学成果和外展模式将主要通过在同行评议的期刊上发表、国际和平协会和学生在专业会议上的发言以及强大的网络方法来传播。

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.