Figure 1. Non-Genetic Membrane Engineering Approaches to Direct Intercellular Interactions.

Several non-genetic methods for cell membrane modification have been used to direct cell-cell interactions. (A) Hydrophobic groups will spontaneously insert into the lipid bilayer, tethering any conjugated cargo or ligands to the cell surface. (B) Functional groups naturally present on the cell surface can be reacted with chemical moieties to covalently tether a variety of species; in many cases, biotin is installed and streptavidin is used as a “bridge” to link other ligands to the cell surface. (C) Liposomes bearing various functional groups can be spontaneously fused with the cell membrane, thereby decorating the surface with the respective modifications. (D) Cells can be grown in media supplemented with functionalized sugar analogs, enabling the incorporation of bioorthogonal groups into surface glycoproteins; these groups can then be conjugated to exogenous ligands. (E) Enzymes can be used to modify naturally-existing proteins and glycans on the cell surface, creating divergent isoforms or tethering synthetic targeting elements.