Hydrophobic Polyelectrolyte: Surface Activity and Membrane Binding

نویسندگان

  • James L. Thomas
  • Scott W. Barton
  • David A. Tirrell
چکیده

We have previously observed that the hydrophobic polyeleclyte poly(2-ethylacryfic aad) solubilizes lipid mnembranes in a pH-dependent manner, and we have explited this phenomenon to prepare lipid vesicles that release their contents in response to pH, light, or glucose (Thomas, J. L., and D. A. Tirrell. Acc. Chem. Res. 25:336-342, 1992.) The physical basis for the interacfion between poly(2-ethylacrylic acid) and lipid membranes has been explored using surface tensionetry and fluorimetry. Varying the polymer concentration results in changes in surface activity and membrane binding that correlate with shifts in the citcal pH for mermbrane solubilization. Furthermore, the binding affinity is reduced as the amount of bound polymer increases. These results are consistent with a hydrophobically driven micellization process, similar to those observed with apolipoproteins, melittin, and other amphiphilic a-helix-based polypeptides. The absence of specific secondary strure in the synthetic polymer suggests that amphiphilicity, rather than sbtrcture, is the most important factor in membrane micellization by macromflecules. INTRODUCTION The ability ofmacromolecules to control membrane structure or permeability is of central importance in biology and biomimetic chemistry. Synthetic polymers are currently used to modify membrane properties in liposomal drug delivery systems (Needham et al., 1992) and to enhance the rate ofmembrane permeation by hydrophobic fluorescent dyes. The hydrophobic polyacid poly(2-ethylacrylic acid) (PEAA, 1) exhibits a pH-dependent interaction with biological membranes: it acts as a molecular switch, permeabilizing and solubilizing membranes at slightly acid pH (pH -6.3), while having no effect at alkaline pH (Thomas and Tirrell, 1992). This "environmentally sensitive" membrane control has potential applications in therapeutics and biosensors.

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تاریخ انتشار 2005