Design and construction of higher-order structure and function in proteinosome-based protocells.

The design and construction of higher-order structure and function in proteinosome microcompartments enclosed by a cross-linked membrane of amphiphilic bovine serum albumin/poly(N-isopropylacrylamide) (BSA-NH2/PNIPAAm) nanoconjugates is described. Three structure/function relationships are investigated: (i) differential chemical cross-linking for the control of membrane disassembly and regulated release of encapsulated genetic polymers; (ii) enzyme-mediated hydrogel structuring of the internal microenvironment to increase mechanical robustness and generate a molecularly crowded reaction environment; and (iii) self-production of a membrane-enclosing outer hydrogel wall for generating protease-resistant forms of the protein-polymer protocells. Our results highlight the potential of integrating aspects of supramolecular and polymer chemistry into the design and construction of novel bioinspired microcompartments as a step toward small-scale materials systems based on synthetic cellularity.