A model system for scattering studies of membrane proteins. (News Briefs).

Because of the difficulty in crystallizing membrane proteins, there is considerable interest in identifying systems that mimic biological membranes and facilitate structural studies of inserted proteins. Solutions of lipidrich mixtures of phospholipids with certain detergents have shown promise in this regard. Over a range of conditions, these mixtures form isolated bilayer fragments that are stabilized by the segregation of the detergent molecules at the edges. The interior of these disk-shaped single-bilayer structures thus provides an environment for guest proteins that is topologically and chemically similar to that of cell membranes. It has also been possible to insert chelated magnetic ions into the bilayer fragments to align the bilayer normals parallel to an applied field, which in turn can be used to orient the fragments, and any inserted proteins, for a scattering experiment.

To assess the potential of using magnetically-doped, mixed lipid bilayers for structural studies of membrane proteins, we have carried out extensive small-angle neutron scattering (SANS) measurements of the morphology, phase behavior, and magnetic alignment of phospholipid detergent mixtures. These data have revealed a previously unrecognized phase at temperatures above 40 [degrees]C in which the bilayer fragments coalesce to form extended single-bilayer sheets. In this phase, the sheets readily align in moderate fields. Measurements in the aligned state reveal that the bilayer sheets are not homogeneous but have defects, probably due to perforations lined with the short chain detergent molecules. By reducing the detergent fraction by about 30%, we have extended the region of stability of this phase to physiologic temperatures while maintaining its basic structure and degree of alignment.

Protocols for inserting membrane proteins in this, the most promising membrane support system identified so far, are currently being developed to enable SANS measurements of the conformation the proteins have in actual cell membranes.

CONTACTS: Mu-Ping Nieh, [phone]; [e-mail] or Charles Glinka, [phone]; [e-mail].