Making Soft Magnetically-Orientable Membranes: An Alternative to Bicelles

Abstract

Model lipid membranes have long been employed in a variety of biophysical techniques to circumvent the complexity of natural membranes when studying their constituents or interactions. The development of magnetically-oriented bilayers, such as DMPC/DHPC bicelles, has been notably important in solid-state NMR where they facilitate the study of membrane interactions, or provide valuable information on the structure and orientation of membrane peptides. Bicelles can be prepared through PC bilayer stabilisation by a variety of detergents, providing that physicochemical requirements are met by adjusting detergent to lipid ratio, concentration, and temperature. In this work we propose an alternative to bicelles, obtained by softening PC liposomes with a gentle surfactant. We show that polysorbate 80 (Tween 80) mixed to DMPC and DPPC bilayers leads to elongated oriented structures which maintain their alignment over a wide range of lipid-to-detergent molar ratios (2<q<13) and temperatures (∼25-80oC), as demonstrated by 31P and 2H solid-state NMR. The orientation quality of these “elastosomes”, determined by spectral simulations, is comparable to traditional bicelles, although they display a different morphology. Moreover, we show that the magnetic orientation can also be flipped by addition of lanthanides, and that transmembrane peptides can be studied. The Tween-based approach for oriented model membranes preparation is promising, and it should in principle be applicable to membrane bilayers of higher complexity - including native membranes - thus bridging the gap between model and intact membranes.