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

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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.