Is the fluid mosaic (and the accompanying raft hypothesis) a suitable model to describe fundamental features of biological membranes? What may be missing?

Abstract

The structure, dynamics, and stability of lipid bilayers are controlled by thermodynamic forces, leading to overall tensionless membranes with a distinct lateral organization and a conspicuous lateral pressure profile. Bilayers are also subject to built-in curvature-stress instabilities that may be released locally or globally in terms of morphological changes leading to the formation of non-lamellar and curved structures. A key controller of the bilayer's propensity to form curved structures is the average molecular shape of the different lipid molecules. Via the curvature stress, molecular shape mediates a coupling to membrane-protein function and provides a set of physical mechanisms for formation of lipid domains and laterally differentiated regions in the plane of the membrane. Unfortunately, these relevant physical features of membranes are often ignored in the most popular models for biological membranes. Results from a number of experimental and theoretical studies emphasize the significance of these fundamental physical properties and call for a refinement of the fluid mosaic model (and the accompanying raft hypothesis).

Keywords: fluid mosaic model; membrane compositional fluctuations; membrane curvature; membrane domains; membrane lateral organization; membrane lateral pressure profile; raft hypothesis.

FIGURE 1

Schematic illustrations of: (A) the lateral pressure profile, p(z), of a lipid bilayer, revealing regions of expansive (positive) pressures and regions of large tensile (negative) pressures; (B) lamellar and non-lamellar lipid aggregates formed by self-assembly processes in water. The different structures have different senses of curvature and are arranged in accordance with the value of the phenomenological molecular packing parameter P; (C) Lipid monolayers with positive, zero, and negative (from top to bottom) curvature determined by the shape of the lipid molecules. Stable lipid bilayer (center) formed by two opposing lipid monolayers. If the monolayers were not constrained by being in the bilayer, they may curve as shown at the top and the bottom illustrations. In the latest cases, the stable bilayer would suffer from a built-in curvature stress. Adapted from Mouritsen (2011a) with permission.

FIGURE 2

Confocal fluorescence images of natural membranes showing micrometer-sized domains. Left: skin stratum corneum lipids membranes from human. This specialized membrane contains 11 different ceramides, cholesterol, and long chain (C₂₄–C₂₆) fatty acids in a ~1:0.9:0.4 mol ratio, and displays coexistence of two gel-like phases (Plasencia et al., 2007). The membrane is labeled with DiIC₁₈, T = 32°C (which represent skin physiological temperature. Right: pulmonary surfactant membranes from pig. This specialized membrane is mainly composed of phospholipids and small amounts of specifically associated proteins (SP-B and SP-C). Among the phospholipids, significant amounts of dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol are present, both of which are unusual species in most animal membranes. Mono-unsaturated phosphatidylcholines (PC), phosphatidylinositol, and neutral lipids including cholesterol are also present in varying proportions (Bernardino de la Serna et al., 2004). This natural membrane is labeled with DiIC₁₈ (red) and Bodipy-PC (green) and is displaying coexistence of lo and ld-like phases, T = 37°C. Scale bars are 10μm.