Biomimetic Metal Bridging Drives Dynamic Protocell-to-Tissue Transitions

In the research on bottom-up construction of protocells and prototissue systems, how to controllably assemble functionalized protocells into prototype tissues with spatial order and collective behavior and achieve dynamic regulation like living systems remains a core challenge. Inspired by the natural mineralization behavior of microorganisms to achieve group organization, this study successfully achieved a leap from individual protocells to dynamic response-type prototype tissues. We first constructed DOPC@ATP/PDDA protocells surface-modified with DSPE-PEG-ALN (DPA), and multivalent metal ions served as "molecular bridges" to enable protocells to spontaneously aggregate and form prototissues. The surface mineralization process formed a nanoscale phosphate crystal layer at the protocell interface, significantly reducing membrane fluidity while retaining semipermeability to small molecule substrates. By embedding glucose oxidase/urease inside the protocells, we achieved local pH regulation through enzyme-mediated internal chemical reactions, thereby triggering reversible cycles of protocells and prototissues. The prototype tissue model constructed in this study not only reproduces the group intelligent regulation behavior of microorganisms using inorganic/organic interfaces but also provides a platform and idea for the development of intelligent drug delivery systems, tissue engineering materials, and understanding the early organizational transition of life.