CAREER: Mechanics of Biological Motor Control: Assembly, Maturation, and Repair at the Neuromuscular Interface

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

This Faculty Early Career Development (CAREER) grant will advance fundamental understanding of the tissues that produce voluntary movement in humans and other biological creatures. These tissues, termed the biological motor control system, help humans navigate unpredictable and dynamic environments by controlling the actuation of skeletal muscle with motor neurons. Health, mobility, and quality-of-life can be severely impacted when disease or damage disrupts the function of skeletal muscle, or motor neurons, or the mechanical communication between these cells. There is thus a significant need to develop model systems that enable study of how mechanical signaling between skeletal muscle and motor neurons impacts performance. This project will conduct experiments that study how mechanical signals drive the assembly of healthy mature neuromuscular tissues through exercise, and how mechanical signaling can guide repair after damage. Developing the proposed model systems will be enabled by new biofabrication tools and protocols for building complex three-dimensional tissues from living cells. The research goals of this project are coupled to educational and outreach goals that promote hands-on training in biofabrication for K-12 and adult learners, with an emphasis on broadening access to experiential self-learning for students from marginalized backgrounds. The specific goal of the research is to understand how exercise coordinates intercellular signaling at the neuromuscular interface in both physiological and pathological states. Uncovering the processes by which mechanically-mediated biochemical signaling coordinates assembly, maturation, and repair at the neuromuscular junction could enable application-driven research in both medicine and soft robotics. Engineered models of the biological motor control system could, for example, be used to enable high-throughput testing of new therapies that restore health and quality-of-life to patients in need. Fabricating contractile neuromuscular tissues could also enable deploying these systems as adaptive and efficient actuators in soft robots. This project will enable the PI to advance the knowledge base in mechanics and biology, establishing the foundation for a long-term career in biofabrication. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.