A. L. Rockwell

Conformations of model peptides in membrane-mimetic environments.

The influence of a membrane environment on the conformational energetics of a polypeptide chain has been investigated through studies of model peptides in a variety of membrane-mimetic media. Nuclear magnetic resonance (NMR) and circular dichroism (CD) data have been obtained for the peptides in bulk hydrophobic solvents, normal micelles, and reversed micelles. Several hydrophobic peptides which are sparingly soluble in water have been solubilized in aqueous sodium dodecyl sulfate (SDS) solution. NMR and CD data indicate that the micelle-solubilized peptides experience an environment with the conformational impact of bulk methanol, and have decreased conformational freedom. The site of residence of the peptides interacting with the micelles appears to be near the surfactant head groups, in a region permeated by water, and not in the micelle core. Strongly hydrophilic peptides have been solubilized in nonpolar solvents by reversed micelles. These peptides are located in small water pools in close association with the head groups of the surfactant. NMR and CD data show that there is a conformational impact of this interfacial water region on peptide solubilizates distinct from that of bulk water.

Exploring Peptide Interactions with Interfacial Water Using Reversed Micelles

Water adjacent to biological membranes or macromolecules has properties distinct from bulk water. Many biological processes such as energy transduction or recognition events occur in this interfacial water region. It is critical to understanding these processes that the nature of interactions between polypeptide chains and the interfacial water be elucidated. Water within reversed micelles shows behavior very similar to this biochemically important interfacial water. The small water pools offer an excellent system for studying interfacial water, since there is no large pool of bulk water to obscure the parameters due to the interfacial water. We have been exploring the interactions of polypeptides with interfacial water by solubilizing synthetic model peptides in Aerosol OT (AOT, sodium bis-2-ethylhexyl-sulfosuccinate) reversed micelles and using nuclear magnetic resonance (NMR) and circular dichroism (CD) to analyze the conformations of the peptides. Our results indicate that the model peptides undergo a conformational change in the interfacial water that is induced by the counterions of the AOT headgroups. CD, 1H and 13c NMR parameters enable conformational monitoring of the peptide upon variation of the amount of water in the internal pools. Furthermore, the influence of the presence of the model peptide in the water pool on the state of the water has been explored using NMR and infrared (IR) spectroscopies. We have found evidence of the perturbation of an amount of water that can be qualitatively related to the nature and size of the surface of the solubilized peptide. These results show promise of using reversed micelles to study polypeptide hydration.