Photomanipulation of Minimal Synthetic Cells: Area Increase, Softening, and Interleaflet Coupling of Membrane Models Doped with Azobenzene‐Lipid Photoswitches

Light can effectively interrogate biological systems in a reversible and physiologically compatible manner with high spatiotemporal precision. Understanding the biophysics of photo‐induced processes in bio‐systems is crucial for achieving relevant clinical applications. Employing membranes doped with the photolipid azobenzene‐phosphatidylcholine (azo‐PC), a holistic picture of light‐triggered changes in membrane kinetics, morphology, and material properties obtained from correlative studies on cell‐sized vesicles, Langmuir monolayers, supported lipid bilayers, and molecular dynamics simulations is provided. Light‐induced membrane area increases as high as ≈25% and a ten‐fold decrease in the membrane bending rigidity is observed upon trans‐to‐cis azo‐PC isomerization associated with membrane leaflet coupling and molecular curvature changes. Vesicle electrodeformation measurements and atomic force microscopy reveal that trans azo‐PC bilayers are thicker than palmitoyl‐oleoyl phosphatidylcholine (POPC) bilayers but have higher specific membrane capacitance and dielectric constant suggesting an increased ability to store electric charges across the membrane. Lastly, incubating POPC vesicles with azo‐PC solutions results in the insertion of azo‐PC in the membrane enabling them to become photoresponsive. All these results demonstrate that light can be used to finely manipulate the shape, mechanical and electric properties of photolipid‐doped minimal cell models, and liposomal drug carriers, thus, presenting a promising therapeutic alternative for the repair of cellular disorders.