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

这项学院早期职业发展(Career)赠款将促进对在人类和其他生物中产生自愿运动的组织的基本了解。这些组织被称为生物运动控制系统，通过控制运动神经元对骨骼肌的驱动，帮助人类在不可预测的动态环境中导航。当疾病或损伤扰乱骨骼肌或运动神经元的功能或这些细胞之间的机械通讯时，健康、行动能力和生活质量都会受到严重影响。因此，有必要开发能够研究骨骼肌和运动神经元之间的机械信号如何影响性能的模型系统。这个项目将进行实验，研究机械信号如何通过运动驱动健康的成熟神经肌肉组织的组装，以及机械信号如何引导损伤后的修复。新的生物制造工具和协议将使开发拟议的模型系统成为可能，以便从活细胞构建复杂的三维组织。这个项目的研究目标与教育和推广目标相结合，这些目标促进了K-12和成人学习者在生物制造方面的动手培训，重点是扩大来自边缘背景的学生进行体验式自学的机会。研究的具体目标是了解运动如何在生理和病理状态下协调神经肌肉界面上的细胞间信号。揭示机械介导的生化信号协调神经肌肉连接处组装、成熟和修复的过程，可以使医学和软机器人领域的应用驱动研究成为可能。例如，生物马达控制系统的工程模型可以用来实现对新疗法的高通量测试，以恢复有需要的患者的健康和生活质量。制造可收缩的神经肌肉组织也可以使这些系统成为软机器人中自适应和高效的执行器。该项目将使PI能够推进力学和生物学方面的知识基础，为长期从事生物工程奠定基础。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.