Photo-manipulation of lipid droplets in synthetic membranes

Abstract

This project aims to develop and characterize photoresponsive vesicles for the controlled release of lipid droplets. These vesicles are composed of conventional lipids (1-palmitoyl-2-oleoyl-glycerol-3-phosphocholine and 1,2-dioleoyl-sn-glycerol-3-phosphocholine) doped with a photoswitchable lipid-like molecule (1-stearoyl-2-[(E)-4-(4-((4-butylphenyl)diazenyl)phenyl)butanoyl]-sn-glycerol-3-phosphocholine), which confers light-responsive properties. Specifically, the vesicles reversibly react to a specific wavelength of light, altering their membrane area, tension, and mechanical properties. When incubated with lipid droplets composed of triolein (glyceryl trioleate), these droplets integrate into the vesicle membrane. Since membrane tension regulates lipid droplet release, the photoswitchable properties enable precise spatial and temporal control over this process. To achieve and monitor such controlled manipulation, advanced methodologies—including confocal fluorescence microscopy and microfluidic techniques—are employed.One of the principal findings of this study is that photoswitchable vesicles containing integrated droplets exhibit light-induced changes in membrane tension, and this modulation of tension leads to significant alterations in droplet behavior. Vesicle tension can be controlled either by light or osmotically. Depending on the osmolarity and light conditions, lipid droplets can exhibit pronounced flattening followed by a reversible transition to a spherical shape. In certain cases, this process leads to the complete release of the lipid droplets from the membrane. Furthermore, membrane asymmetry influences the probability of detachment, and budding directionality is favored by lower surface tension in one of the leaflets. By combining lipid droplets with photoresponsive vesicles, this research provides insights into lipid droplet emergence and detachment in cellular homeostasis and opens new avenues for innovative applications in photopharmacology.