Revealing the effect of membrane curvature on lipid-mediated Ras clustering using nanostructures

Abstract

As the plasma membrane of cells is inelastic and does not bend spontaneously, membrane curvature is an active process mediated by specialized proteins, lipids and the cytoskeleton. Membrane curvature plays a crucial role for changes in cell shape during cell migration, division and programmed cell death. One of the key membrane proteins that manages the key MAPK pathway known as Ras proteins, are commonly mutated and locked in an active state in cancer, disturbing the usual cell cycle and leading to carcinogenesis. It was discovered that different Ras isoforms form distinct and laterally segregated nanoclusters on the inner layers of the plasma membrane depending on the local lipid composition. As the local lipid composition may also affect the membrane curvature, there is an intriguing question whether Ras nanoclustering depends on the membrane curvature as well. By using fabricated arrays of nanobars to induce controlled plasma membrane curvature on a nanoscale level, the curvature responses of Ras isoforms and lipids were studied to better understand the biomechanisms of the plasma membrane in cancer cells.