Influence of Local Cytoskeletal Plasticity on Neuronal Cell Mechanics

该奖项的研究目标是研究神经元中的力传递与神经元细胞骨架之间的基本关系，神经元细胞骨架是一种相互连接的丝状结构网络，在决定神经元形态和稳定性方面发挥着关键作用。特别是，拉伸载荷（拉伸）的作用，对区域变形的细胞骨架将进行研究。该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。关键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，响应张力的细胞骨架移动性和稳定性的空间和时间变化的表征，以及细胞骨架细丝和交联分子马达蛋白在指导细胞骨架重塑中的作用的阐述。这项工作将对理解发育和成熟的外周神经系统的结构-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，这项工作有可能为神经系统疾病（如腕管综合征）的进展或增强神经修复提供机制基础。还预计，从神经元工作中确定的一般原则将有助于理解非神经元细胞中的细胞骨架可塑性。教育和推广计划的重点是将研究成果纳入基于细胞生理学的两门生物工程课程，并为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，暑期外展计划将使来自科学和工程背景的中学生接触生物工程的职业选择，向他们介绍研究方法和科学写作，并为他们提供最先进的实验室设施。

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.