Differential scanning calorimetry and X-ray diffraction studies of the specificity of the interaction of antimicrobial peptides with membrane-mimeticsystems

Interest in biophysical studies on the interaction of antimicrobial peptide s and lipids has strongly increased because of the rapid emergence of antib iotic-resistant bacterial strains. An understanding of the molecular mechan ism(s) of membrane perturbation by these peptides will allow a design of no vel peptide antibiotics as an alternative to conventional antibiotics. Diff erential scanning calorimetry and X-ray diffraction studies have yielded a wealth of quantitative information on the effects of antimicrobial peptides on membrane structure as well as on peptide location. These studies clearl y demonstrated that antimicrobial peptides show preferential interaction wi th specific phospholipid classes. Furthermore, they revealed that in additi on to charge-charge interactions, membrane curvature strain and hydrophobic mismatch between peptides and lipids are important parameters in determini ng the mechanism of membrane perturbation. Hence, depending on the molecula r properties of both lipid and peptide, creation of bilayer defects such as phase separation or membrane thinning, pore formation, promotion of nonlam ellar lipid structures or bilayer disruption by the carpet model or deterge nt-like action, may occur. Moreover, these studies suggest that these diffe rent processes may represent gradual steps of membrane perturbation. A bett er understanding of the mutual dependence of these parameters will help to elucidate the molecular mechanism of membrane damage by antimicrobial pepti des and their target membrane specificity, keys for the rationale design of novel types of peptide antibiotics. (C) 1999 Elsevier Science B.V. All rig hts reserved.