Programmed assembly of 3-dimensional microtissues with defined cellular connectivity

摘要: Multicellular organs comprise differentiated cell types with discrete yet interdependent functions. The cells' spatial arrangements and interconnectivities, both critical elements of higher-order function, derive from complex developmental programs in vivo are often difficult or impossible to emulate vitro. Here, we report the bottom-up synthesis microtissues composed multiple programmed connectivity. We functionalized cells short oligonucleotides impart specific adhesive properties. Hybridization complementary DNA sequences enabled assembly multicellular structures defined cell–cell contacts. demonstrated that kinetic parameters process depend on sequence complexity, density, total concentration. Thus, can be highly controlled, enabling design composition stoichiometry. used this strategy construct a paracrine signaling network isolated 3-dimensional microtissues.