In this project the PI will investigate the hypothesis that there is a fundamental set of nanoscale physical and biochemical properties that serve as the primary cues for the re-establishment of cell systems that rely on nanofibrillar scaffolds in their native environment, and they will use an integrated approach for their investigation. A novel investigative tool, scanning probe recognition microscopy, will be used in concert with state of the art immunocytochemistry, fluorescent microscopy and blot techniques in an integrated physics-cell biology effort that links the physical properties at the nanoscale with important cellular responses. Results from this research are likely to have a major impact on regenerative medicine aimed at recreating the neural cell system following central nervous system injury. Furthermore, as cell systems that are influenced by scaffold-based environments are ubiquitous throughout the body, identification of the fundamental set of nanoscale properties that promote healthy neural cell physiology and function, serves as the basis for the quantitative exploration of other regenerative cell-scaffold systems. The research program will be realized with active student participation. Regular exchange visits, joint training, and regular communication, with evaluation and dissemination of results, will contribute to the multidisciplinary training. The proposed pipeline program for the introduction of traditionally underrepresented undergraduates within the research, in collaboration with the mentored MI-LSAMP and RISE programs, will build on the PI,s successful experiences with both.