Traction force and tension fluctuations in growing axons

Abstract

Actively generated mechanical forces play a central role in axon growth and guidance, but the mechanisms that underly force generation and regulation in growing axons remain poorly understood. We report measurements of the dynamics of traction stresses from growth cones of actively advancing axons from postnatal rat DRG neurons. By tracking the movement of the growth cone and analyzing the traction stress field from a reference frame that moves with it, we are able to show that there is a clear and consistent average stress field that underlies the complex spatial stresses present at any one time. The average stress field has strong maxima on the sides of the growth cone, directed inward toward the growth cone neck. This pattern represents a contractile stress contained within the growth cone, and a net force that is balanced by the axon tension. Using high time-resolution measurements of the growth cone traction stresses, we show that the stress field is composed of fluctuating local stress peaks, with a large number peaks that live for a short time, a population of peaks whose lifetime distribution follows an exponential decay, and a small number of very long-lived peaks. We show that the high time-resolution data also reveal that the tension appears to vary randomly over short time scales, roughly consistent with the lifetime of the stress peaks, suggesting that the tension fluctuations originate from stochastic adhesion dynamics.