Plasma membranes of living cells are compartmentalized into small sub-microscopic structures (nanodomains) with potentially relevant biological functions. Despite this fact very little is known about these nanodomains, mainly due to difficulties to characterize such small dynamic entities.
For instance, it is totally unclear whether nanodomains found in the upper bilayer leaflet are transversally registered with those found in the lower leaflet. Experiments performed on large microscopically sized domains indicate that coupling between the leaflets is strong, forcing the domains to be in perfect registration.
But can the same thing be said about biologically more relevant nanodomains? This work provides an experimental evidence that even the small nanodomains of variable sizes between 10 and 160 nm are inter-leaflet coupled. Importantly, the remaining scenarios of partially registered, independent or anti-registered nanodomains could unambiguously be excluded.