Transient directed motions of GABAA receptors in growth cones detected by a speed correlation index

Single-molecule tracking of membrane proteins has become an important tool for investigating dynamic processes in live cells, such as cell signaling, membrane compartmentation or trafficking. The extraction of relevant parameters, such as interaction times between molecular partners or confinement-zone sizes, from the trajectories of single molecules requires appropriate statistical methods. Here we report a new tool, the speed correlation index, designed to detect transient periods of directed motion within trajectories of diffusing molecules. The ability to detect such events in a wide range of biologically relevant parameter values (speed, diffusion coefficient, and durations of the directed period) was first established on simulated data. The method was next applied to analyze the trajectories of quantum-dot-labeled GABA(A) receptors in nerve growth cones. The use of the speed correlation index revealed that the receptors had a "conveyor belt" type of motion due to temporary interactions (similar to 4.0 s) between the receptors and the microtubules, leading to an average directed motion (velocity similar to 0.3 mu m s(-1)) in the growth-cone membrane. Our observations point to the possibility of a cytoskeleton-dependent redistribution of the sensing molecules in the membrane, which could play a role in the modulation of the cell response to external signals.