Dr. George Lykotrafitis, an assistant professor of Mechanical Engineering and Biomedical Engineering, seeks to tease out the mysteries, at the nanometer scale, of how sodium and potassium ion channels are distributed within axons of live neurons and to reveal how the arrangement of these channels affects the action potential – or messaging ability – of neurons, which play a central role in the nervous systems of all living things. The research, funded by a five-year National Science Foundation Early Career Development (CAREER) Award, may help researchers better understand how signals propagate in neurons and pathways leading to epilepsy and neurodegenerative diseases such as Alzheimer’s.
Neurons are a vital part of the nervous system, which comprises not only the brain and central nervous system but also the spinal cord and ganglia. They are responsible for the transmission of information throughout the body via chemical and electrical signals. Axons are long, tendril-like cells that link neurons and transport information away from the neuron.
Using atomic force microscopy (AFM) and toxin pharmacology, Lykotrafitis will examine the spatial organization of voltage-gated sodium and potassium ion channels in the unmyelinated, or unsheathed, axon of a live neuron at the nanometer scale to understand how the spatial arrangement of these electrolyte channels affects nerve transmission. Both types of ion channels play critical roles in regulating the nervous system. Potassium channels are especially complex and regulate functions such as heart rate, insulin secretion and muscle contraction.
For each type of ion channel, Lykotrafitis said, “We will perform AFM scans of the axon of a rat hippocampal neuron using a cantilever tip functionalized with a specific toxin under physiological conditions to determine the spatial distribution of the channel. Using electrophysiology – in other words, measuring the electrical activity within the neuron – we will gauge the effect of cortical cytoskeleton disruption on the initiation and propagation of the action potential, the process by which neuron cells communicate. The combination of these two techniques will improve our understanding of how the spatial distribution and function of ion channels determine the propagation of the action potential.”
Lykotrafitis notes that an essential component of the project is the development of an extensive particle-based computational model that will integrate electrochemistry with the structural mechanics of the axon and the distribution of sodium and potassium channels. The model will simulate the formation and propagation of an action potential along the axon and will allow a better understanding of the complexity involved in this phenomenon and how defects in the structure of the axon influence the function of neurons.
“We are planning to develop an agent-based model merged with coarse-grained molecular dynamics techniques as a new approach in the study of signal propagation in neurons,” he says.
Debilitating diseases have long been the focus of Lykotrafitis’ research. In recent years he has set his sights on understanding how interactions between cellular biomechanical properties and subcellular structures influence the severity of sickle cell disease (SCD), with the objective of enhancing diagnoses, pharmacotherapy and prevention of life threatening complications. His CAREER research will extend the scope of his scholarly program and establish an invaluable platform for advanced biomedical engineering graduate student research and education.