Asymmetric lipid membranes: towards more realistic model systems

Abstract

Despite the ubiquity of transbilayer asymmetry in natural cell membranes, the vast majority of existing research has utilized chemically well-defined symmetric liposomes, where the inner and outer bilayer leaflets have the same composition. Here, we review various aspects of asymmetry in nature and in model systems in anticipation for the next phase of model membrane studies.

Figure 1

Proposed distribution of phospholipids in human red blood cells put forward by Verkleij et al. [4].

Figure 2

Asymmetric lipid distribution due to vesicle size. Data were generated using the area per lipid and bilayer thickness of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) as determined by Kučerka and co-workers [34].

Figure 3

Cartoon illustration of differently-shaped lipids and the associated curvature.

Figure 4

Schematic of asymmetric vesicle construction methods. The left is a schematic of cyclodextrin-mediated lipid exchange of the outer membrane leaflet [10]. The right-hand scheme is the engineering of asymmetric vesicles generated by two independently prepared monolayers [54].

Figure 5

Putative transbilayer coupling mechanisms in asymmetric lipid membranes. $\left(\mathbf{\text{A}}\right)$ Asymmetric lipids containing fatty acid chains of differing length have been observed to interdigitate; $\left(\mathbf{\text{B}}\right)$ Trans-bilayer cholesterol (Chol) movement; $\left(\mathbf{\text{C}}\right)$ the ordered leaflet induces order to the less ordered leaflet; $\left(\mathbf{\text{D}}\right)$ the area per lipid of one leaflet influences the area per lipid of the other, and vice versa. Such an area difference can arise from lipid species or charge differences between monolayers; $\left(\mathbf{\text{E}}\right)$ Curvature and/or microemulsion in one leaflet can be transferred to the other.

Figure 6

Energy profile for Chol flip/flop. The red arrow indicates that the barrier for flip/flop decreases as membrane disorder increases, as reported in [83,84].

Figure 7

Schematic of an integral protein orienting itself according to electrostatic attraction between positive domains on the protein and negatively-charged lipids on the inner leaflet.