Inter-protocellular macromolecular communication via nanoparticle-induced gap-junction mimics

Multicellular organisms rely on cell-cell contacts and substance exchange via transmembrane channels such as gap-junctions to maintain their biological behavior. Despite substantial advances in protocell-environment signaling, key challenges persist in developing synthetic channels that mimic the natural gap-junctions for macromolecular transport in protocells. Here, we developed an electrostatic interaction-based strategy for constructing nanoparticle-mediated gap-junction mimics in the membrane of protocells, investigating electrostatic modulation of membrane integrity and subsequent transmembrane signaling regulation. By engineering interactions between charged nanoparticles and protocell membrane, we modulated the contact and higher-order assembly behavior of protocells. We also achieved molecular weight-dependent and concentration gradient-controlled directional transmembrane transport of macromolecular signals between protocells. Further integrating molecular dynamics simulations with experimental validation, we systematically deciphered nanoparticle-membrane interaction dynamics and established the mechanism of electrostatic regulation in transmembrane communication. In summary, this study offers promising insights into the physical principles underlying transmembrane signaling and establishes a foundation for constructing synthetic cellular networks with advanced macromolecular communication functionalities.