Leading edges have stiffer edges (red).

Fox/Elsevier

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...

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