A Depolymerization Based Model of Neuron Growth Cone Shape and Motility

Cell migration is a ubiquitous process underlying critical biological mechanisms like wound healing, cancer metastasis and even neuron growth cone motility. It is a critical process for the living organisms as it ensures proper functioning of the system, for example, crawling fibroblasts endure closure of wounds during wound healing. Here we focus our interest on neuron growth cones, a sensory and motile organelle present at the tip of extending neurites, like the axons, in neurons. These are responsible for neuron pathfinding onto specific targets and synapses, in responses to various guidance cues. Interestingly, the motility of the growth cones is characterized by a crawling mechanism comparable to other eukaryotic cells. The focus of this project is to quantify the effect of actin filament depolymerization, by the actin disassembly protein Cofilin, on the shape and motility of the neuron axonal growth cones. Results predict an experimentally-testable hypothesis of an increase in growth cone speed and change in shape with an increase in the depolymerization rate. This is indicative of contractile force generation through depolymerization that aids in growth cone motility. The model suggests a paradigm for force generation in actin-based crawling cells which should be applicable to many different cells. Cell migration is a ubiquitous process underlying critical biological mechanisms like wound healing, cancer metastasis and even neuron growth cone motility. It is a critical process for the living organisms as it ensures proper functioning of the system, for example, crawling fibroblasts endure closure of wounds during wound healing. Here we focus our interest on neuron growth cones, a sensory and motile organelle present at the tip of extending neurites, like the axons, in neurons. These are responsible for neuron pathfinding onto specific targets and synapses, in responses to various guidance cues. Interestingly, the motility of the growth cones is characterized by a crawling mechanism comparable to other eukaryotic cells. The focus of this project is to quantify the effect of actin filament depolymerization, by the actin disassembly protein Cofilin, on the shape and motility of the neuron axonal growth cones. Results predict an experimentally-testable hypothesis of an increase in growth cone speed and change in shape with an increase in the depolymerization rate. This is indicative of contractile force generation through depolymerization that aids in growth cone motility. The model suggests a paradigm for force generation in actin-based crawling cells which should be applicable to many different cells