Nanophotonic tools to resolve nanoscale dynamics on biological membranes

The plasma membrane of living cells is dynamically compartmentalized at multiple spatial scales ranging from the nano- to the mesoscale. This compartmentalization is crucial for a large number of cellular functions as it allows different receptors and proteins to efficiently interact, in space and time, with their partner ligands and to trigger cell signaling events. At the nanoscale, cell membranes organize into dynamic nano-assemblies known as lipid rafts, enriched by cholesterol, sphingolipids, and certain types of proteins. However, despite many years of research, the field of lipid rafts has remained elusive given their small size (nanometer scale) and their transient character. Visualizing lipid rafts in living cells thus requires simultaneous nanometer spatial precision and microsecond temporal resolution, which is beyond the reach of diffraction-limited optical microscopy. Optical antennas based on metallic nanostructures efficiently enhance and confine light into nanometer dimensions, breaching the diffraction limit. I will discuss recent progress from our group combining optical antennas with fluorescence correlation spectroscopy (FCS) to enquire on the nanoscale dynamics of multicomponent lipid bilayers and living cells. Our results reveal the coexistence of cholesterol-enriched fluctuating nanoscopic domains on mimetic and living cell membranes, in the microsecond scale and with characteristic sizes below 10nm. These nanoscale assemblies might represent lipid raft precursors that in the absence of proteins and/or other molecular stabilizing factors, are poised to be highly transient.