PHASE-SEPARATION IN PHOSPHOLIPID-BILAYERS INDUCED BY BIOLOGICALLY-ACTIVE POLYCATIONS

The interaction of various polyionenes with phospholipid bilayer membranes was explored by means of differential scanning calorimetry (DSC) with special reference to their antimicrobial activities. A strong interaction was observed between the polyionenes and acidic phospholipids, whereas zwitterionic phospholipid bilayers were not affected significantly by the polycations. Addition of the polyionenes was found to result in phase separation in mixed bilayer membranes composed of acidic and zwitterionic phospholipids. The ability to induce phase separation strongly depended on the structure of the polyionenes. Polyionenes with rigid spacers were found to be most effective to induce phase separation and to be most active in antimicrobial activity. Polyionenes with rigid and flexible spacers in the alternate fashion exhibited less activities which were similar to those of all flexible spacers. Furthermore, their mode of interaction with bilayers was again similar to those of all flexible spacers. Our results indicate that the rigid spacers are favorable for strong interaction with membranes which are assumed to be the target sites of the polycationic biocides, leading to the higher activity. Other factors affecting both the antimicrobial activity and the mode of interaction with membranes were molecular weight and hydrophobicity. With increasing molecular weight, both the activity and ability to induce phase separation increased. Introduction of hydrophilic groups into the spacers resulted in loss of activity and ability to induce phase separation. The antimicrobial activity and the mode of interaction with membranes were correlated and interpreted on the basis of conformational concept of the polyionenes in solution. © 1990.