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Abstract:
Lysophosphatidic acid (LPA) is a serum-borne lipid mediator that binds to a variety of different G protein-coupled receptors to trigger an exceptionally wide range of biological effects, including cell survival and differentiation, cancer cell migration, and embryonic development. Here we synthesized caged LPA (cgLPA), a "photolysable" coumarin-masked derivative of LPA. We demonstrate that illumination of cgLPA with 405 nm light liberates bioactive LPA on a subsecond scale to evoke Ca(2+) signaling, Rho activation, and cytoskeletal contraction. In addition, we developed an "optotaxis" assay to attract melanoma cells through a stable chemotactic gradient by repeated liberation of LPA through local photolysis of extracellular cgLPA. We expect that this method of light-controlled chemotaxis will be generally applicable to a large variety of small molecules that drive cellular migration or other responses.
