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

University Of Connecticut, Storrs CT

Investigators

Abstract

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.