Cholesterol-based anchors and tethers for phospholipid bilayers and for model biological membranes

Abstract

This review covers the range of cholesterol-based anchors and tethers and the ways in which they are being used. These cholesterol conjugates provide us with a very flexible ‘tool-box’ that can be used to tether phospholipid bilayers to surfaces, to join bilayers together (bilayer-to-bilayer, bilayer-to-vesicle, vesicle-to-vesicle, etc.) or to anchor molecules, biomolecules, macromolecules or particulate species to the surface of the bilayer. Model biomembranes tethered to a solid support provide a stable platform for addressing membrane components in vitro using force field and spectroscopic methods and since these membranes generally remain fluid and retain much of their biological activity, solid-supported membranes can also be use to study aspects of membrane biology and biochemistry. Potential medical applications are developing out of our ability to anchor ‘markers’ and antibodies to phospholipid vesicles. Compared to anchors in which the anchoring group is a phospholipid (or phospholipid-like) moiety, cholesterol-based anchors are generally easier to make and purify but the anchoring is less strong and this can be an issue when the ‘payload’ is large and water-soluble. In the case of nucleic acid functionalised systems this problem has been addressed by anchoring each oligonucleotide through two cholesteryl end-groups.