The molecular basis of biological motility

Motility of class X myosin (green) along fascin-actin bundles (red)

Living organisms rely on their ability to move and reshape themselves when needed. A wide variety of motions, including muscle contraction, vesicle transport, and cell division, are driven by molecular machines that exert an amazing amount of force considering that they are only a few nanometers across. Due to their central role in biology, motor proteins have been studied extensively using a broad range of biochemical and biophysical approaches. Frustratingly, these efforts have just scratched the surface and many of the most fundamental questions remain unresolved. To take an example, nonmuscle myosins are known to traffic various cargoes on the actin cytoskeleton. How does a myosin identify the correct actin filament to move along, given the enormous number of filaments that point in every direction? It is clear that without guidance cues motors would traffic components to the wrong destination, with disastrous consequences for cellular organization.

The work in my lab uses advanced single-molecule assays to watch myosin motor proteins and the actin cytoskeleton at work. We label them with fluorescent probes to watch them move in real time, and we use optical traps to push or pull on them as they move. Using these techniques, we can set up situations that typical myosin motor would encounter in a cell, where multiple types of motors and tracks cooperate or compete. We are also applying our single-molecule to study trafficking patterns in whole cells.