Computer model: investigating role of filopodia-based steering in experimental neurite galvanotropism.

Since early in this century developing axons and dendrites in culture have been reported to grow along electric field lines. It is only in the last score of years, however, that evidence suggests developing neurites actually orient in response to the electrical stimulus. We are interested in how an imposed electric field appears to speed neurite outgrowth in a field-related direction. We ask the question whether enhanced outgrowth in one direction results from streamlining outgrowth in that direction or from differentially catalysing the rate of outgrowth. Evidence for possible mechanisms of such neurite galvanotropism includes an electric field-dependent redistribution of filopodia, the finger-like structures that extend from the growing neurite tip. Using simple rules based on filopodia-mediated substrate sampling and orientation of extending neurites in vitro, we have built a computer model to test the streamlining theory. This in silico model of non-branching neurite outgrowth in two dimensions possesses the capacity to apportion its sampling efforts relative to a fixed reference representing the orientation of the field lines of a steady uniform electric field. Our model suggests that simple outgrowth patterns observed for experimental neurite galvanotropism-deflected and enhanced neurite growth toward the negative electrode and reduced neurite growth directed toward the positive electrode-may be simulated by tipping the balance of filopodia in the direction of the negative electrode. The existence of an analogous pattern-generating interaction between an applied electric field and extending neuronal processes would suggest a role for endogenous fields arising from naturally occurring potential gradients in developing organisms.