Leading edges have stiffer edges (red).


Cell migration depends on polarized actin polymerization at a cell's front edge. To get the most out of these actin networks, plasma membrane flexibility must be similarly polarized, according to results from Amit Vasanji, Paul Fox (Cleveland Clinic Foundation, Cleveland, OH), and colleagues.

The group shows that the membrane is stiffest at the front of migrating endothelial cells. This oriented flexibility is fine-tuned through cholesterol distribution. Growth factors that induce migration in vascular cells caused cholesterol to concentrate at the leading edge, and this gradient was needed for migration. In liposomes, addition of a modest amount of cholesterol (thus creating a stiffer membrane) promoted the ability of actin to deform the membrane.

One might expect a flexible membrane to be more easily moved by polymerizing actin, but Fox compares actin in a cholesterol-free cell to a finger pressed into a balloon. “It's so flexible,” he says, “a filament gets completely surrounded. There's no room for more monomers to come in. With some stiffness, [a filament] pushes forward a section [of membrane] that leaves room for more actin.” The effect may be compounded by the exclusion of bundling and cross-linking proteins. This theory is supported by the authors' findings that growth factors stabilize the forward actin network. The group next hopes to determine how growth factors orient cholesterol trafficking, possibly through transport proteins such as caveolin-1. ▪


Vasanji, A., et al.
Dev. Cell.