Effects of amphipathic polypeptides on membrane organization inferred from studies using bicellar lipid mixtures.

SP-B63-78, a lung surfactant protein fragment, and magainin 2, an antimicrobial peptide, are amphipathic peptides with the same overall charge but different biological functions. Deuterium nuclear magnetic resonance has been used to compare the interactions of these peptides with dispersions of 1,2-dimyristoyl-sn-glycero-3-phophocholine (DMPC)/1,2-dihexanoyl-sn-glycero-3-phophocholine (DHPC) (4:1) and DMPC/1,2-dimyristoyl-sn-glycero-3-phopho-(1'-rac-glycerol) (DMPG)/DHPC (3 : 1 : 1 ), two mixtures of long-chain and short-chain lipids that display bicellar behavior. This study exploited the sensitivity of a bicellar system structural organization to factors that modify partitioning of their lipid components between different environments. In small bicelle particles formed at low temperatures, short-chain components preferentially occupy curved rim environments around bilayer disks of the long-chain components. Changes in chain order and lipid mixing, on heating, can drive transitions to more extended assemblies including a magnetically orientable phase at intermediate temperature. In this work, neither peptide had a substantial effect on the behavior of the zwitterionic DMPC/DHPC mixture. For bicellar mixtures containing the anionic lipid DMPG, the peptide SP-B63-78 lowered the temperature at which magnetically orientable particles coalesced into more extended lamellar structures. SP-B63-78 did not promote partitioning of the zwitterionic and anionic longchain lipid components into different environments. Magainin 2, on the other hand, was found to promote separation of the anionic lipid, DMPG, and the zwitterionic lipid, DMPC, into different environments for temperatures above 34 degrees C. The contrast between the effects of these two peptides on the lipid mixtures studied appears to be consistent with their functional roles in biological systems.