Optical Control of Lipid Rafts with Photoswitchable Ceramides

Ceramide is a pro-apoptotic sphingolipid with unique physical characteristics. Often viewed as a second messenger, its generation can modulate the structure of lipid rafts. We prepared three photoswitchable ceramides, ACes, which contain an azobenzene photoswitch allowing for optical control over the N-acyl chain. Using combined atomic force and confocal fluorescence microscopy, we demonstrate that the ACes enable reversible switching of lipid domains in raft-mimicking supported lipid bilayers (SLBs). In the trans-configuration, the ACes localize into the liquid-ordered (L_o) phase. Photoisomerization to the cis-form triggers a fluidification of the L_o domains, as liquid-disordered (L_d) "lakes" are formed within the rafts. Photoisomerization back to the trans-state with blue light stimulates a rigidification inside the L_d phase, as the formation of small L_o domains. These changes can be repeated over multiple cycles, enabling a dynamic spatiotemporal control of the lipid raft structure with light.