Light-Triggered Decoding of Hydrophobic Interactions in Living Systems

Abstract

The hydrophobic effect is central to biological organization, underlying membrane assembly, molecular recognition, and protein folding. Despite its importance, spatiotemporal control of hydrophobicity is challenging because it emerges from collective solvation free-energy effects around hydrocarbon frameworks whose C(sp3)–H bonds are chemically inert. Here we show that hydrophobic interactions can be encoded and decoded on demand under physiological conditions using water-soluble functional groups and visible light. Aliphatic carbon frameworks are encoded in charged radical precursors, significantly reducing the free-energy penalty of aqueous solvation. Light-triggered single-electron decarboxylation converts these precursors into nonpolar hydrocarbon products, restoring hydrophobic interactions. This transition drives emergent behaviors including membrane self-assembly, lipid-mediated signaling, and targeted protein degradation in living cells.