Deciphering small molecule diffusion parameters across light responsive polymersome membranes

Biological membranes orchestrate compartmentalization and selective transport to sustain out-of-equilibrium processes in living systems. Mimicking these dual roles with synthetic materials requires membranes that combine robustness with programmable permeability. Here, we report a systematic study of light-responsive polymersomes in which Donor–Acceptor Stenhouse Adducts (DASAs) embedded in the hydrophobic leaflet act as photoswitchable regulators of molecular transport. A library of five amphiphilic block copolymers bearing increasing densities of DASA moieties was synthesized and self-assembled into vesicular membranes. Using spectroscopic, calorimetric, and cryo-EM techniques, we show that the degree of functionalization critically dictates both photoswitching efficiency and small-molecule permeation. Importantly, polymersomes functionalized with ~10% DASAs exhibited the highest light-induced release rates, whereas higher densities reduced responsiveness due to inner filter effects, increased membrane thickness, and reduced free volume for isomerization. This work provides a comparative framework for understanding how functional group density governs polymersome transport properties. By revealing design principles for balancing stability, responsiveness, and permeability, our findings establish guidelines for engineering stimuli-responsive synthetic compartments as synthetic cells and nanoreactors with applications in biotechnology and therapeutics.