(62bj) Metabolically Controlled 3D Cellular Integration Into Lipid Silica Films

We have discovered a unique metabolically and optically controlled lithography approach that allows patterned integration of live cells into nominally solid-state devices and maintains their viability under extreme conditions of desiccation and starvation. We observe that yeast, bacterial, and mammalian cells deposited on lipid/silica thin film mesophases actively reconstruct the surface to create a fully 3D bio/nano interface composed of localized lipid bilayers enveloped by a lipid /silica mesophase. Remarkably this integration process selects exclusively for living cells over the corresponding apoptotic cells. The localized lipid interface maintains fluidity, accessibility, and functionality of the cellular surface and viability of the cell as we show, for example, by exposure of an immobilized mammalian immune cell to a model endotoxin, lipopolysaccharide (LPS) from E coli. Recognition of LPS by cell surface receptors activates the Toll-like receptor 4 (TL-4) signaling pathway, confirming functions including molecular recognition, recruiting of adaptor molecules, activation of kinases, etc. Optical definition of cellular integration is achieved by dose-dependent UV exposure of the lipid/silica mesophase film. Short exposures reduce the film contact angle with water and promote integration. Longer exposures solidify the lipid/silica mesophase, preventing integration. Double exposures define first patterns of cellular integration and second high diffusivity pathways to or between cells via photolytic degradation of the lipid mesophase template and attendant formation of ordered monosized, mesopores. Temperature dependent studies along with those employing sodium azide to interfere with ATP production confirm that integration is metabolically controlled. Biaxial stress measurements reveal that integration is accompanied by a low frequency oscillatory stress that is communicated between and appears to synchronize the behaviors of the integrating cells. Auxiliary nanocomponents added to the lipid/silica mesophase film or introduced with the cell are localized at the cellular surface. Overall this ?lithography with life' approach provides the first demonstration of optically-defined 3D cellular immobilization. It promises a new means to integrate ?bio' with ?nano' into platforms useful to study and manipulate cellular behavior at the individual cell level and to interface living organisms with electronics, photonics, and fluidics.