Unexpected Cholesterol-Induced Destabilization of Lipid Membranes near Transmembrane Carbon Nanotubes

Abstract

Cholesterol is a crucial component of mammalian cell membranes that takes part in many vital processes. It is generally accepted that cholesterol stabilizes the membrane and induces transitions into ordered states. In contrast to expectations, we demonstrate that cholesterol can destabilize the membrane by creating a nanodomain around a perpendicularly embedded ultrashort carbon nanotube (CNT), and we show that cholesterol triggers the translocation of an ultrashort CNT through the cell membrane. Using atomistic simulations, we report the existence of a nanoscale domain around an ultrashort carbon nanotube within a crossover distance of 0.9nm from the surface of the nanotube, where the properties of the bilayer are different from the bulk: the domain is characterized by increased fluctuations, increased thickness, and increased order of the lipids with respect to the bulk. Cholesterol decreases the thickness and order of lipids and increases the fluctuations with respect to a pure lipid bilayer. Experimentally, we confirm that cholesterol nanodomains provoke spontaneous translocation of nanotubes through a lipid bilayer even for low membrane tensions. A specially designed microfluidic device allows us to trace the kinetic pathway of the translocation process and establish the threshold cholesterol concentration of 20% for translocation. The reported nanoscale cholesterol-induced membrane restructuring near the ultrashort CNT in lipid membranes enables precise control and specific targeting of a membrane using cholesterol. As an example, it may allow for specific targeting between cholesterol-rich mammalian cells and cholesterol-poor bacterial cells.