Insertion
of Amphipathic Helices into Membranes Depends on the Spontaneous Curvature of
the Lipid System
Erik Strandberg,
Karlsruhe Institute of
Technology,
The antimicrobial peptide MSI-103 forms an amphipathic a-helix when binding to a lipid membrane. The orientation of the helix in the membrane can be determined with high accuracy using 2H solid-state NMR. In the present study the orientation of MSI-103 was determined in a wide range of lipid systems with varying properties. In phosphatidylcholine (PC) bilayers with different acyl chains, there was no correlation between chain length and peptide orientation. However, a distinct difference was observed in the peptide response to saturated and unsaturated acyl chains. In unsaturated lipids, the peptide always remained in the surface-bound S-state, with its a-helical axis perpendicular to the bilayer normal at a tilt angle close to 90o. Only in saturated lipids it was able to insert into the membrane in a tilted T-state, with a tilt angle of around 125o. Interestingly, when lyso-PC was added, the T-state was found to be stable also in unsaturated lipids.
These results can be explained by the shape of the lipids; especially the relative cross-sectional area of head groups and acyl chains, which is related to the spontaneous curvature. In systems with negative spontaneous curvature, the head group area is small relative to the acyl chain area, and in such systems, peptides are always found in the S-state. In systems with positive spontaneous curvature, peptides are found in a T-state at higher concentration.
Interestingly, we found that the presence of cholesterol prevents MSI-103 from binding to the membrane in any ordered state, but rather induces the formation of immobilized peptide aggregates. This observation can essentially explain the selective membrane-permeabilizing action of MSI-103 on bacteria compared to eukaryotic cells which contain cholesterol.