Statistical analysis of neuronal growth: edge dynamics and the effect of a focused laser on growth cone motility

The neuronal growth cone is a small dynamic structure at the tip of neuronal extensions that guides each neurite extension to its correct partner cell. To reach the designated target, the growth cone integrates chemical signals with high accuracy and reliability. This signal detection operates close to the thermal noise limit and is, therefore of high interest not only to understand neuronal growth, but also to investigate the biological mechanisms of signalling and information processing under the influence of noise. To further investigate neuronal growth, a focused laser positioned at the leading edge of the growth cone is used to bias growth direction, however, the mechanisms of this influence are still unclear. We present a detailed measurement and analysis of the leading edge dynamics of laser treated and control growth cones. Based on the edge motility measurements, we can consistently describe neuronal growth with a stochastic model that allows a bistable potential and the noise intensity of the stochastic process to be extracted. The investigation of control growth cones that were not influenced by the laser reveals a nonlinear dependence of the noise on the overall activity of the growth cones. The presented analysis further quantifies the edge dynamics in growth cones that are manipulated by a laser. Growth cones that actively follow the laser show a tilt of the bistable potential in the direction of the laser to favour protrusions, but no significant changes in the leading edge growth velocity. This is in contrast to the potential changes observed in stationary growth cones that were influenced by the laser. Here, the laser does not tilt the potential shape, but increases the edge velocities, probably by an increase in actin polymerization velocity. These measurements provide new quantitative insight into the dynamics underlying growth cone protrusion and movement