MEMBRANE SOLUBILIZATION BY A HYDROPHOBIC POLYELECTROLYTE - SURFACE-ACTIVITY AND MEMBRANE-BINDING

We have previously observed that the hydrophobic polyelectrolyte poly( 2-ethylacrylic acid) solubilizes lipid membranes in a pH-dependent man ner, and we have exploited this phenomenon to prepare lipid vesicles t hat release their contents in response to pH, light, or glucose (Thoma s, J. L., and D. A. Tirrell. Ace. Chem. Res. 25:336-342, 1992.) The ph ysical basis for the interaction between poly(2-ethylacrylic acid) and lipid membranes has been explored using surface tensiometry and fluor imetry. Varying the polymer concentration results in changes in surfac e activity and membrane binding that correlate with shifts in the crit ical pH for membrane solubilization. Furthermore, the binding affinity is reduced as the amount of bound polymer increases. These results ar e consistent with a hydrophobically driven micellization process, simi lar to those observed with apolipoproteins, melittin, and other amphip hilic alpha-helix-based polypeptides. The absence of specific secondar y structure in the synthetic polymer suggests that amphiphilicity, rat her than structure, is the most important factor in membrane micelliza tion by macromolecules.