Cyclical content exchange in hydrogel-core synthetic cells

Abstract

Synthetic cells lack the complex protein machinery that living cells use to control molecular traffic across their membranes, making programmable exchange with the environment a central challenge in bottom-up synthetic biology. Here, we introduce a protein-free approach for dynamic content exchange in liposome-based synthetic cells through a membrane-hydrogel composite architecture. We assemble the synthetic cell by crosslinking a polymer hydrogel within the lumen of giant unilamellar vesicles (GUVs) and chemically tethering it to the inner membrane leaflet. The resulting mechanical coupling enables a previously unexplored response through which the membrane can be reversibly permeabilized and re-sealed upon osmotic swelling and de-swelling of the hydrogel. This mechanism of membrane remodeling enables cyclic exchange of small molecules and macromolecules, offering a versatile route for dynamic regulation of intracellular biochemistry that does not rely on reconstituted protein pores.