CAREER: Agent-based Modeling of Action Potential Initiation and Propagation in Unmyelinated Neurons

该学院早期职业发展计划奖的研究目标是在纳米尺度上揭示活神经元无髓轴突中电压门控钠钾通道的空间组织，并研究这些通道的空间排列如何决定动作电位的特性。原子力显微镜结合毒素药理学将用于离子通道的检测。对于每种类型的离子通道，在正常情况下，将用带有相应特定毒素的悬臂尖端扫描大鼠海马神经元的轴突。利用电生理学，我们将测量大脑皮层细胞骨架破坏对动作电位的启动和传播的影响。为了了解离子通道的空间组织如何决定动作电位的性质，将在基于试剂的建模框架内使用粗粒分子动力学和电化学。该项目的成功完成将为定量理解动作电位的生物力学基础开辟新的途径。引入基于智能体的建模作为模拟生物化学和细胞功能之间联系的通用框架，将允许对细胞的动态行为进行建模，如细胞运动和对信号的响应。该教育计划包括开发一门基于试剂的建模研究生课程，重点是细胞力学，并将原子力显微镜纳入机械工程实验技术的本科课程。将建立一个非正式小组，以促进研究人员和对神经力学感兴趣的学生之间的跨学科互动。由该奖项产生的计算和实验项目将被纳入工程学院多样性计划，以在高中教师和学生中促进工程和科学，包括来自当地高中的代表不足的少数民族学生。

The research objective of this Faculty Early Career Development (CAREER) Program award is to reveal the spatial organization of voltage-gated sodium and potassium channels in the unmyelinated axon of a living neuron at the nanometer scale and to investigate how the spatial arrangement of these channels determines the properties of the action potential. Atomic force microscopy combined with toxin pharmacology will be employed for ion channel detection. For each type of ion channel, the axon of a rat hippocampal neuron will be scanned with a cantilever tip functionalized with the corresponding specific toxin under normal conditions. By using electrophysiology, the effect of cortical cytoskeleton disruption on the initiation and propagation of the action potential will be measured. To understand how the spatial organization of ion channels determines the action potential properties, coarse-grain molecular dynamics and electrochemistry, within the framework of agent-based modeling, will be used.Successful completion of this project will open new avenues in quantitatively understanding the biomechanical basis of the action potential. The introduction of agent-based modeling as a general framework for simulating the connection between biochemistry and cell function will allow for modeling of dynamic behaviors of cells such as cell motility and response to signaling. The educational program includes the development of a graduate course on agent-based modeling with emphasis on cell mechanics and the incorporation of atomic force microscopy in an undergraduate class of experimental techniques in mechanical engineering. An informal group will be established to promote cross-disciplinary interaction between researchers and students interested in neuronal mechanics. Computational and experimental projects stemming from this award will be incorporated in the School of Engineering Diversity Program to promote engineering and science among high school teachers and students, including underrepresented minority students from local high schools.