Proc. Natl. Acad. Sci. USA 111, 5896–5901 (2014)

The ability to manipulate the start and end point of a cell's migratory journey is an important tool for biological and therapeutic studies. However, co-opting the cell's chemotaxic machinery to promote directed movement remains difficult owing to the presence of signals in the cellular environment that can either misdirect or inhibit movement. As an alternative, Park et al. devised an approach using a modified G protein–coupled receptor (RASSL) that responds specifically to the biologically inert small molecule clozapine-N-oxide (CNO). Neutrophils transfected with the RASSL receptor exhibited cytoskeletal changes in response to CNO treatment and migrate toward a micropipette-generated gradient of CNO. The authors found that this system was applicable for a variety of cell types such as keratinocytes and endothelial cells, and neutrophils and T lymphocytes were shown to undergo trans-endothelial migration through a monolayer to reach the CNO signal. Finally, the RASSL system could be used in vivo, where intravenously administered RASSL-expressing T lymphocytes could localize to a microsphere releasing CNO. Overall, this RASSL-CNO system could be an interesting approach to direct cells to particular cellular destinations.