On the shape of migrating cells — a `front-to-back' model

Abstract

The wide range of shapes that are seen in stationary animal cells is believed to be the result of an interplay between giant filamentous complexes – largely the microfilaments and microtubules – although how this is achieved is unknown. In a migrating cell these large elements are also important, but here I suggest an additional factor: the cell surface distribution of those molecules that attach the cell to the substratum. As an animal cell advances, the attachments it makes with the substratum necessarily move backwards with respect to the cell. A fresh supply of these attachments – usually integrin molecules – is required at the cell front so that new attachments can be made. This supply is believed to be provided by the endocytic cycle, which enables the collection of integrins and other molecules from elsewhere on the surface of the cell to be recirculated to the front end of the cell. The rate at which a particular integrin cycles will determine its distribution on the ventral surface of the cell and this, in turn, might help to determine the shape of the cell. I also propose that adhesion molecules that have a slow rate of cycling will produce a flattish phenotype, as seen in fibroblasts, whereas a more rapid cycling will lead to a more snail-like shape. In addition, this model suggests why membrane ruffling occurs and that large non-circulating surface molecules move towards the back of the cell where they might assist in detaching the back end of the cell.