Photoregulated Assembly–Disassembly Dynamics of Interfering with Organelle Membrane Integrity

Assembly–disassembly dynamics driven by fuel-driven out-of-equilibrium processes play a key role in biological function. Here, we present a photoregulated assembly–disassembly dynamic system based on synthetic building blocks composed of an azobenzene moiety and an organelle membrane-targeting unit. Upon localization to the organelle membrane, these photoresponsive monomers self-assemble into supramolecular fibrils that interact multivalently with the membrane. UV irradiation (365 nm) induces trans-to-cis isomerization of the azobenzene units, resulting in a morphological transition from fibrillar to amorphous assemblies with reduced membrane affinity. Subsequent exposure to visible light (450 nm) restores the fibrillar state. This reversible assembly–disassembly process enables dynamic control of the membrane binding strength, ultimately disrupting organelle membrane integrity through cyclic weakening and strengthening of supramolecular interactions. Our findings highlight the potential of light-driven, multivalent self-assembly as a strategy for modulating subcellular structures and regulating cellular fate with high spatial and temporal precision.