Influence of Local Cytoskeletal Plasticity on Neuronal Cell Mechanics

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The research objective of this award is to investigate fundamental relationships between force transmission in neurons and the neuronal cytoskeleton, an interconnected filamentous structural network that plays a key role in determining neuronal morphology and stability. In particular, the role of tensile loading (stretch) on the regional deformation of the cytoskeleton will be investigated. The study will involve a multidisciplinary approach, integrating cell biomechanics, high-resolution imaging, and image processing. Key outcomes include the definition of spatial and temporal distributions of tension within unstretched and stretched axons, the characterization of spatial and temporal changes in cytoskeletal mobility and stability in response to tension, and the elaboration of a role for cytoskeletal filaments and crosslinking molecular motor proteins in guiding cytoskeletal remodeling.If successful, this work will have significant implications for understanding structure-function relationships in the developing and mature peripheral nervous system, including potential biological and chemical signaling pathways triggered by local deformation. In the long-term, this work holds the potential to provide a mechanistic basis for the progression of neurological conditions such as carpal tunnel syndrome, or enhancing nerve repair. It is also expected that general principles identified from work in neurons will facilitate the understanding of cytoskeletal plasticity in non-neuronal cells. The educational and outreach plans focus on the integration of research results into two bioengineering courses based on cell physiology, as well as providing multidisciplinary research training opportunities for undergraduate and graduate students from backgrounds in both engineering and biological sciences. Additionally, a summer outreach program will expose middle and high school students from backgrounds underrepresented in science and engineering to career options in bioengineering, introduce them to research methodology and scientific writing, and provide them with access to state-of-the-art laboratory facilities.