Molecular interactions with bilayer membrane stacks using neutron and X-ray diffraction

Lamellar unit cell reconstruction from neutron and X-ray diffraction data provides information about the disposition and position of molecules and molecular segments with respect to the bilayer. When supplemented with the judicious use of molecular deuteration, the technique probes the molecular interactions and conformations within the bilayer membrane and the water layer which constitute the crystallographic unit cell. The perspective is model independent, and potentially, with a higher degree of resolution than is available with other techniques. In the case of neutron diffraction the measurement consists of carefully normalised diffracted intensity under conditions of contrast variation of the water layer. The subsequent Fourier reconstruction of the unit cell is made using the phase information from variation of peak intensities with contrast. Although the phase problem is not as easily solved for the corresponding X-ray measurements, an intuitive approach can often suffice. Here we discuss the two complimentary techniques as probes of scattering length density profiles of a bilayer, and how such a perspective provides information about the location and orientation of molecules within or between lipid bilayers. Within the basic paradigm of lamellar phases this method has provided, for example, detailed insights into the location and interaction of cryoprotectants and stress proteins, of the mechanisms of actions of viral proteins, antimicrobial compounds and drugs, and the underlying structure of the stratum corneum. In this paper we review these techniques and provide examples of the systems that have been examined. We finish with a future outlook on the use of these techniques to improve our understanding of the interactions of membranes with biomolecules.