Erin Craig (Physics)
Neuroplasticity, the ability for neurons to reorganize and form new connections, has major implications for brain trauma recovery and neurological disorders. During nervous system development, neurons extend long narrow fibers called axons that must grow in the correct direction to form neural connections. The microscopic navigators that lead axon extension are called growth cones. These sensitive motile structures at the tip of axons respond to various chemical cues for navigation. In this study, we develop computer-based models to investigate how growth cones respond to external chemical “traffic signals” and guide axon outgrowth. Our model framework builds on previous studies by assuming that a dense network of dynamic filaments called f-actin operate as the engine of the growth cone vehicle. We use this framework to investigate the less well understood growth cone steering mechanism. We introduce long filaments of dynamic biopolymer proteins termed “exploratory” microtubules (MTs) that extend from the axon into the growth cone, randomly switching between states of growth and shrinkage as they “explore” the growth cone leading-edge. Our leading hypothesis is that microtubules respond to external guidance cues by triggering a biochemical reaction, causing the f-actin growth cone engine to engage. The objective of the current model is to investigate the physical role of the exploratory MTs and the mechanisms that bridge chemotactic cues to growth cone turning. By computationally reconstructing the mechanics of the growth cone, we are addressing an essential step to understanding the underlying causes of neurological diseases.
Keywords: Neuroscience, Cytoskeleton, Morphogenesis