Photoregulated Assembly-Disassembly Dynamics of Interfering with Organelle Membrane Integrity.

Abstract

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 <i>trans</i>-to-<i>cis</i> 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.