Lipodisks

Planar membrane structures, best described as bilayer disks, may be found in mixtures of phospholipids and various micelle-forming components. In many cases the disks are merely short-lived intermediates formed during a phase- or structural transition. Examples are the circular, or sometimes more irregular, membrane patches frequently observed during surfactant mediated solubilization of liposomes. We have discovered that particularly stable, and close to perfectly circular disks can form in dilute aqueous solutions containing a mixture of lipids and polyethyleneglycol-conjugated lipids (PEG-lipids).

Schematic pictures showing the difference in structure between liposomes (A) and lipid disks (B). Illustration to the right (C) shows a cross-sectional view of a PEG-stabilized lipid disks.

PEG-lipids are routinely used in order to prolong the blood circulation time of liposomes used for drug delivery applications. It is well established that upon inclusion of sufficiently high concentrations of PEG-lipids a transition from bilayer to micellar phase occurs. Further, our systematic studies of the phase behaviour and aggregate structure in various lipid/PEG-lipid systems have revealed that either cylindrical or disk-shaped micelles may form as the bilayer saturation concentration is exceeded. The results from cryo-TEM investigations show that discoidal structures are preferred over cylindrical micelles when the lipid mixture contains components that reduce the spontaneous curvature and increase the monolayer bending modulus. Such components are e.g. cholesterol, lanosterol and DSPE. Discoidal structures are furthermore preferred at temperatures below the TC of the lipid mixture. In this case, disk formation is likely promoted by a combination of high bending modulus and reduced lipid:PEG-lipid miscibility.

Aggregate structure as revealed by cryo-TEM in lipid/PEG-lipid systems.
A) liposomes, B) bilayer discs, and C) coexistence between liposomes and thread-like cylindrical micelles.

The size of the disks is critically dependent on the PEG-lipid concentration. Large disks, more accurately described as circular membrane patches, are found at PEG-lipid concentrations just above the bilayer saturation limit. With increasing PEG-lipid concentration the size of the disks decreases. Investigations based on a combination of dynamic light scattering, SANS and cryo-TEM verify that the disks are well described by an ideal disk model assuming partial component segregation. More precisely, available data strongly suggest that the PEG-lipids accumulate at the highly curved rim of the disks while the phospholipids, and cholesterol, reside in the bulk of the bilayer aggregates. The PEG-stabilized lipodisks show excellent long term stability and their size and structure remains unaltered over a wide temperature range. In addition, results from several studies show that membrane proteins can be successfully reconstituted into the disks.

We are investigating several biochemical, biotechnical and pharmaceutical applications of the lipodisks. Besides studies focused on the utilization of lipodisks as model membranes, we have ongoing projects directed towards the use of the disks as carriers for, e.g., poorly soluble drugs and antimicrobial peptides.