Artificial nanotube connections and transport of molecular cargo between mammalian cells

Lipid nanotubes interconnecting mammalian cells, sometimes referred to as tunneling nanotubes, have recently received increased attention, as their importance in intercellular transport and communication has been recognized. We present a set of microfabrication procedures for the deliberate formation of intercellular nanotube links between single mammalian cells, employing microneedle manipulation protocols, developed earlier for nanotube-vesicle networks. Cell-to-cell connections were established, and their effectiveness for intercellular transport of molecular cargo was demonstrated. We initiate transport of Ca2+ ions and fluorescein diphosphate, a prefluorescent enzyme substrate, between cells, and demonstrate the validity and effectiveness of artificially created nanotube connections for cell-to-cell communication. We thus provide a new experimental model for probing cell-to-cell communication, which we deem the foundation for man-made network architectures involving biological cells. This model can greatly facilitate fundamental studies of cell-to-cell communication modes, the exchange of cell constituents and components, and the dynamics of biochemical reactions in native network environments.