Photosensitizer binding to lipid bilayers as a precondition for the photoinactivation of membrane channels

The photodynamic activity of sulfonated aluminum phthalocyanines (AIPcS(n), 1 less than or equal to n less than or equal to 4) was found to correlate with their affinity for membrane lipids. Adsorbing to the surface of large unilamellar vesicles (LUVs), aluminum phthalocyanine disulfonate induced th e highest changes in their electrophoretic mobility. AlPcS2, was also most efficient in mediating photoinactivation of gramicidin channels, as reveale d by measurements of the electric current across planar lipid bilayers. The increase in the degree of sulfonation of phthalocyanine progressively redu ced its affinity for the lipid bilayer as well as its potency of sensitizin g gramicidin channel photoinactivation. The portion of photoinactivated gra micidin channels, alpha, increased with rising photosensitizer concentratio n up to some optimum. The concentration at which alpha was at half-maximum amounted to 80 nM, 30 nM, 200 nM, and 2 mu M for AlPcS1, AlPcS2, AlPcS3, an d AlPcS4, respectively. At high concentrations cu was found to decrease, wh ich was attributed to quenching of reactive oxygen species and self-quenchi ng of the photosensitizer triplet state by its ground state. Fluoride anion s were observed to inhibit both AlPcSn (2 less than or equal to n less than or equal to 4) binding to LUVs and sensitized photoinactivation of gramici din channels. It is concluded that photosensitizer binding to membrane lipi ds is a prerequisite for the photodynamic inactivation of gramicidin channe ls.