A model of neurite extension across regions of nonpermissive substrate: simulations based on experimental measurement of growth cone motility and filopodial dynamics

Abstract

The guidance of pioneer neurites in the developing embryo occurs through a variety of mechanisms, including chemotaxis, haptotaxis, contact inhibition, and mechanical guidance. In each of these processes, the growth cone serves as a sensory-motile mediator of the neurite response to a directional cue. However, the role of growth cone dynamics in determining the neurite path is not well-defined. To provide a quantitative basis for investigating this relationship, we have developed a mathematical model that describes two major aspects of growth cone motility during neurite outgrowth: the continuous but erratic motion frequently observed on homogeneous substrates such as laminin or collagen and the more directed movement along filopodial that have contacted a remote cue. Model parameters include the rate and angle of filopodial initiation, rates of filopodial extension and retraction, maximum filopodial length, and the root-mean square speed and directional persistence time of growth cone advance. Experimental estimates of these parameters were obtained from in vitro measurements on chick dorsal root ganglion and rat superior cervical ganglion neurons and used to compare model results with previously reported experimental data for neurite outgrowth on a patterned laminin/albumin substrate. The model represents a conceptual framework for further investigation and elucidation of the role of growth cone dynamics in neurite outgrowth and guidance.