Meyer says this idea “was really from watching cells in the microscope and seeing how they make direction changes. It was more consistent with stochastic, small turns than the cell knowing where the signal is located.” The biased random walk was driven by local lamellipod extensions, correlated with PI3P pulses, that spanned only a fraction of the total leading edge. Furthermore, the actions of the left and right of the leading edge were not correlated.
The decision to protrude, Meyer believes, is based only on local chemoattractant binding, so that each receptor ligation triggers a local lamellipod that turns the cell by ∼2 degrees. The steering, then, is just the stochastic difference between multiple small turns toward the left and right. This system “is running on the top of self-polarization at the front of the cell and helping to guide it,” says Meyer.
The distinct self-polarization process is important, however, in defining the front of the cell as the part of the cell that is responsive to turning and extension signals, and in allowing random walking in the absence of a chemotactic gradient. Such random walking increases the range of cells, so that they can reach the areas where chemotactic signals are present to guide their continued travels.
Meyer believes that the self-polarization does involve a global process, and also involves PIP3, but that the process is distinct from steering. He hopes to isolate components that are necessary locally for chemotactic steering but not globally for self-polarization and random migration.