Rewiring Cell Membranes with Bioorthogonal Surface Chemistry for Fundamental and Applied Studies

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The ability to spatially and temporally direct 3-dimensional (3-D) tissue assembly comprised of multiple cell lines is crucial for next generation therapeutic applications in immunity and regenerative medicine. Efficient nucleic acid transfection, In vivo Imaging, tracking and targeted drug delivery to specific cells, cell tissues and drug resistant bacteria is critical for many diagnostic biotechnologies, vaccine development and drug screening platforms. These research fields and markets are diverse but converge at the ability to rewire (engineer) cell surfaces for specific applications. A new general method that rewires cell surfaces with the capability to install any ligand or protein on a cell surface and to also be able to control cell to cell interconnectivity in space and time would allow for unprecedented exploration of a range of fundamental cell behaviour studies and to provide new ways to display imaging probes, advance cell based biotechnologies and accelerate regenerative medicine and tissue engineering based therapies. In this proposal, we will develop a powerful universal strategy that: 1. delivers a range of bio-orthogonal chemical groups via nanotechnology (liposome fusion) to cell surfaces for subsequent in-situ tailoring for on-demand tissue assembly for a range of new biotechnology, transfection and tissue engineering applications and 2. delivers a broad range of ligands or proteins rapidly to cell surfaces without the use of molecular biology or metabolic biosynthesis and 3. a combined cell surface engineering and bioorthogonal chemistry approach to transfect cells with nucleic acid via click chemistry.