Influence of Local Cytoskeletal Plasticity on Neuronal Cell Mechanics

该奖项的研究目标是调查神经元力传递和神经元细胞骨架之间的基本关系，神经元细胞骨架是一个相互连接的丝状结构网络，在决定神经元的形态和稳定性方面发挥着关键作用。特别是，拉伸载荷(拉伸)对细胞骨架的区域变形的作用将被研究。这项研究将涉及多学科方法，整合细胞生物力学、高分辨率成像和图像处理。主要成果包括未拉伸和拉伸轴突内张力的空间和时间分布的定义，细胞骨架对张力响应的流动性和稳定性的时空变化的表征，以及细胞骨架细丝和交联型分子马达蛋白在指导细胞骨架重构中的作用。如果成功，这项工作将对理解发育和成熟的周围神经系统的结构-功能关系，包括由局部变形触发的潜在生物和化学信号通路具有重要意义。从长远来看，这项工作有可能为腕管综合征或加强神经修复等神经系统疾病的进展提供机制基础。从神经元的工作中确定的一般原理也有望有助于理解非神经元细胞中细胞骨架的可塑性。教育和推广计划的重点是将研究成果纳入两门以细胞生理学为基础的生物工程课程，并为具有工程和生物科学背景的本科生和研究生提供多学科研究培训机会。此外，暑期外展计划将向来自科学和工程专业背景不足的初中生和高中生提供生物工程方面的职业选择，向他们介绍研究方法和科学写作，并为他们提供使用最先进的实验室设施的机会。

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.