The design and synthesis of a novel acid‐degradable polyethylene glycol‐based N‐hydroxysuccinimide (NHS) ester‐activated crosslinker is reported. The crosslinker is reactive towards nucleophiles and features a central ketal functional group that is stable at pH > 7.5 and rapidly hydrolyses at pH > 6.0. The crosslinker is used to (i) fabricate acid‐degradable polysaccharide hydrogels that exhibit controlled degradation upon exposure to an acidic environment or via endogenous enzyme activity; and (ii) construct hydrogel‐filled protein‐polymer microcompartments (termed proteinosomes) capable of pH‐dependent membrane disassembly. Taken together the results provide new opportunities for the fabrication of pH‐responsive soft materials with potential applications in drug delivery, tissue engineering, and soft‐matter bioengineering.

The achievement of light‐responsive behaviours is an important target for protocell engineering to allow control of fundamental protocellular processes such as communication via diffusible chemical signals, shape changes or even motility at the flick of a switch. As a step towards this ambitious goal, here we describe the synthesis of a novel poly(ethylene glycol)‐based crosslinker, reactive towards nucleophiles, that effectively degrades with UV light (405 nm). We demonstrate its utility for the fabrication of the first protocell membranes capable of light‐induced disassembly, for the photo‐generation of patterns of protocells, and for the modulation of protocell membrane permeability. Overall, our results not only open up new avenues towards the engineering of spatially organised, communicating networks of protocells, and of micro‐compartmentalised systems for information storage and release, but also have important implications for other research fields such as drug delivery and soft materials chemistry.

Micellar and vesicular photonic compartments capable of reporting the chemical environment as well as introducing user-defined functionalities were successfully constructed.