Importance of the hexagonal lipid phase in biological membrane organization

Abstract

Domains are present in every natural membrane. They are characterized by a distinctive protein and/or lipid composition. Their size is highly variable from the nano- to the micrometer scale. The domains confer specific properties to the membrane leading to original structure and function. The determinants leading to domain organization are therefore important but remain obscure. This review presents how the ability of lipids to organize into hexagonal II or lamellar phases can promote particular local structures within membranes. Since biological membranes are composed of a mixture of lipids, each with distinctive biophysical properties, lateral and transversal sorting of lipids can promote creation of domains inside the membrane through local modulation of the lipid phase. Lipid biophysical properties have been characterized for long based on in vitro analyses using non-natural lipid molecules; their re-examinations using natural lipids might open interesting perspectives on membrane architecture occurring in vivo in various cellular and physiological contexts.

Keywords: glycerolipid; hexagonal phase; lipid bilayers; lipid phase; membrane domains.

FIGURE 1

Shape structure concept of lipid polymorphism. Lipids with a small polar head have a molecular shape that resembles a truncated cone. They induce a negative curvature strain and favor the organization of membranes into inverted micelles (HII phases) or cubic (bicontinuous) structures. Lipids with a bulky polar head and only one acyl chain have a molecular shape similar to an inverted cone and induce a positive curvature strain in membranes. They favor the formation of tubular (HI) or spheric micelles. Lipids that have similar cross-sectional areas for the polar head and hydrophobic region look like cylinders. They form lamellar phases, with no curvature strain.

FIGURE 2

HII phase in bilayers. (A) Lipidic particle as described in (Siegel, 1984). (B) Mechanisms of membrane fusion involving HII via the stalk intermediate. (1) Apposition of two bilayers. (2) Stalk. The stalk is cylindrically symmetrical. (3) Hemifusion intermediate. It can form two different types of structures. If the bilayer diaphragm in the middle of the hemifusion intermediate ruptures, it forms a fusion pore (4) If fusion pores accumulate in sufficient numbers, they can rearrange to form a cubic phase (5) For systems close to the lamellar/HII phase boundary, hemifusion intermediates can also aggregate to form HII phase (6) Figure adapted from Siegel (1999).