MOLECULAR HARPOONS - MEMBRANE-DISRUPTIVE SURFACTANTS THAT CAN RECOGNIZE OSMOTIC-STRESS IN PHOSPHOLIPID-BILAYERS

A series of wedge-shaped, nonionic surfactant molecules (molecular harpoons) have been synthesized and used to disrupt large unilamellar vesicles derived from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), POPC/cholesterol (2/1), and POPC/cholesterol (55/45), under isotonic and hypotonic (osmotically stressed) conditions. The activity of each surfactant has been defined by measuring its ability to release vesicle-encapsulated 5(6)-carboxyfluorescein (CF). Comparative studies have also been carried out, using Triton X-100 as the disruptive agent. The principal results of this study establish that it is possible for a disruptive surfactant to distinguish between osmotically stressed and nonstressed membranes and that such recognition is a sensitive function of the surfactant's composition, structure, and oligomeric state, as well as the compactness of the target membrane and its degree of osmotic stress. The implications of these findings for the rational design of membrane-disrupting antimicrobial agents are briefly discussed.