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* Département de Chimie, Centre de Recherche en Sciences et Ingénierie des Macromolécules, Université Laval, Québec, Québec, Canada, G1K 7P4; and
Institut Européen de Chimie et Biologie, FRE CNRS 2247, 33607 Pessac, France
Correspondence: Address reprint requests to Michèle Auger, Département de Chimie, CERSIM, Université Laval, Québec, Québec, Canada, G1K 7P4. Tel.: 418-656-3393; Fax: 418-656-7916; E-mail: michele.auger{at}chm.ulaval.ca.
The interaction of the neuropeptide methionine-enkephalin (Menk) with bicelles was investigated by solid-state NMR. Bicelles composed of dimyristoylphosphatidylcholine (DMPC) and dicaproylphosphatidylcholine (DCPC) were modified to investigate the effect of the lipid headgroup and electrostatic charges on the association with Menk. A total of 10 mol % of DMPC was replaced by zwitterionic phosphatidylethanolamine (DMPE), anionic phosphatidylglycerol (DMPG), or phosphatidylserine (DMPS). The preparation of DMPE-doped bicelles (Bic/PE) is reported for the first time. The 31P and 2H NMR results revealed changes in the lipid dynamics when Menk interacts with the bicellar systems. 2H NMR experiments showed a disordering effect of Menk on the lipid chains in all the bicelles except Bic/PG, whereas the study of the choline headgroups indicated a decreased order of the lipids only in Bic/PE and Bic/PG. Our results suggest that the insertion depth of Menk into bicelles is modulated by their composition, more specifically by the balance between hydrophobic and electrostatic interactions. Menk would be buried at the lipid polar/apolar interface, the depth of penetration into the hydrophobic membrane core following the scaling Bic > Bic/PE > Bic/PS at the slightly acidic pH used in this study. The peptide would not insert into the bilayer core of Bic/PG and would rather remain at the surface.
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