The bioorthogonal copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction exhibits complex but well-defined kinetics in aqueous and organic solution for soluble azides, alkynes, and ligand-bound copper(I). The kinetic profile in two dimensions, however, for CuAAC systems within a lipid bilayer membrane, has yet to be defined. The effect of triazole formation with lipid membrane-bound components on membrane properties such as fluidity and permeability is also of interest. Using functionalized membranes containing synthetic lipids that have been modified with azide and terminal alkyne moieties, as well as an alkylated copper(I)-binding ligand, kinetics for CuAAC with membrane bound substrates have been evaluated at micromolar concentrations. Additionally, membrane fluidity and permeability following the triazole formation have also been evaluated through a combination of supported lipid bilayers with fluorescent recovery after photobleaching and radiometric calcium flux imaging. Applications of this work include the potential for novel symmetric membrane leaflet labeling, providing a method for bioorthogonal manipulation of cell and tissue function, and creating membranes with precisely controlled properties that are not be available in naturally-occurring membranes.

Chemical modulation of lipid bilayer membranes via copper(I)-catalyzed azide alkyne cycloaddition

249th National Meeting (2015)

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