Nanomechanics of Src signaling in neuronal growth cones

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During development and regeneration of the nervous system, neurons send out processes guided by the neuronal growth cone, a highly motile sensing structure and an excellent model system to study the dynamic interactions between cell surface, signaling, and cytoskeletal proteins such as actin. Although significant progress has been made in identifying the molecules involved in directional growth cone migration, the underlying mechanisms are not well understood. Particularly, the relationship between mechanical and biochemical signaling in neuronal growth and guidance remains a mystery. To fill this knowledge gap, this project will investigate how Src tyrosine kinase, a key signaling enzyme, regulates actin organization and dynamics as well as adhesion-mediated growth and force production of live neurons. Specifically, this project will determine which aspects of actin dynamics are regulated by Src as well as the relationship between force production and Src signaling in adhesion-mediated growth. To reach this goal, quantitative fluorescent imaging of cytoskeletal dynamics and Src activation will be combined with biophysical approaches involving micropipettes and the Atomic Force Microscope (AFM). This research will significantly improve the understanding of how cells integrate sensing, signaling, and cytoskeletal dynamics during directional migration. The project involves training of High School, undergraduate, and graduate students in cutting-edge live cell imaging and biophysical techniques. The results will not only be disseminated to the scientific community, but also to the broad public through a web site called "CELLebration" displaying movies, images, and educational material about cell motility, through presentations at local schools, and public outreach events at Purdue University (Spring Fest and NanoDays). In summary, through high-quality digital imaging presentations, this work will increase the public awareness for the need for quantitative microscopy and biophysical approaches to solve key cell biological problems.