Sizes of lipid domains: What do we know from artificial lipid membranes? What are the possible shared features with membrane rafts in cells?

In model lipid membranes with phase coexistence, domain sizes distribute in a very wide range, from the nanometer (reported in vesicles and supported films) to the micrometer (observed in many model membranes). Domain growth by coalescence and Ostwald ripening is slow (minutes to hours), the domain size being correlated with the size of the capture region. Domain sizes thus strongly depend on the number of domains which, in the case of a nucleation process, depends on the oversaturation of the system, on line tension and on the perturbation rate in relation to the membrane dynamics. Here, an overview is given of the factors that affect nucleation or spinodal decomposition and domain growth, and their influence on the distribution of domain sizes in different model membranes is discussed. The parameters analyzed respond to very general physical rules, and we therefore propose a similar behavior for the rafts in the plasma membrane of cells, but with obstructed mobility and with a continuously changing environment.

Molecular Insight into the Line Tension of Bilayer Membranes Containing Hybrid Polyunsaturated Lipids.

Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was proposed that hybrid lipids, with mixed saturated and unsaturated acyl chains, participate in the relaxation of γ through different mechanisms. In this work, we used molecular dynamics simulations of the coarse-grained MARTINI model to measure γ in liquid-ordered-liquid-disordered (Lo-Ld) membranes, with increasingly larger relative proportion of the hybrid polyunsaturated lipid PAPC (4:0-5:4PC) to DAPC (di5:4PC) (i.e., XH). We also calculated an elastic contribution to γ by the Lo-Ld thickness mismatch, tilt moduli, and bending moduli, as predicted by theory. We found that an increase in XH decreased the overall γ value and the elastic contribution to line tension. The effect on the elastic line tension is driven by a reduced hydrophobic mismatch. Changes in the elastic constants of the phases due to an increase in XH produced a slightly larger elastic γ term. In addition to this elastic energy, other major contributions to γ are found in these model membranes. Increasing XH decreases both elastic and nonelastic contributions to γ. Finally, PAPC also behaves as a linactant, relaxing γ through an interfacial effect, as predicted by theoretical results. This study gives insight into the actual contribution of distinct energy terms to γ in bilayers containing polyunsaturated hybrid lipids.

The self-organization of lipids and proteins of myelin at the membrane interface. Molecular factors underlying the microheterogeneity of domain segregation.

The advances over the last 10 years on the understanding of myelin heterogeneity are reviewed. The main focus is on the applicability of Langmuir monolayers, Langmuir-Blodgett films and some associated techniques to unravelling the behaviour of interfaces formed with all the components of a natural membrane. Lipid-protein lateral segregation appears as a major driving force to determine surface patterns that can change under compression from circular domains to two-dimensional fractal structures. The major proteins of the myelin membrane induce lateral segregation in an otherwise homogeneous surface formed by the mixture of total myelin lipids. The lipid and protein components appear to distribute in the surface domains according to their charge, compressibility and relative molecular weight: myelin proteins, ganglioside GM1 and fluorescent lipid probes partition into liquid-expanded phase domains; other components such as phosphatidylserine and galactocerebroside partition into another liquid phase enriched in cholesterol. Simplified protein-lipid mixtures allow assessment of the participation of the major proteins in the two dimensional pattern development. One of the major myelin proteins, the Folch-Lees proteolipid, self-segregates into, and determines formation of, fractal-like patterns. The presence of the second major protein, myelin basic protein, leads to round liquid-expanded domains in the absence of Folch-Lees proteolipid and softens the boundaries of the fractal structures in its presence. The location of myelin basic protein in the interface is surface pressure sensitive, being slightly squeezed out at high surface pressure, allowing the fractal domains enriched in Folch-Lees proteolipid to evolve.

Composition-driven surface domain structuring mediated by sphingolipids and membrane-active proteins. Above the nano- but under the micro-scale: mesoscopic biochemical/structural cross-talk in biomembranes.

Biomembranes contain a wide variety of lipids and proteins within an essentially two-dimensional structure. The coexistence of such a large number of molecular species causes local tensions that frequently relax into a phase or compositional immiscibility along the lateral and transverse planes of the interface. As a consequence, a substantial microheterogeneity of the surface topography develops and that depends not only on the lipid-protein composition, but also on the lateral and transverse tensions generated as a consequence of molecular interactions. The presence of proteins, and immiscibility among lipids, constitute major perturbing factors for the membrane sculpturing both in terms of its surface topography and dynamics. In this work, we will summarize some recent evidences for the involvement of membrane-associated, both extrinsic and amphitropic, proteins as well as membrane-active phosphohydrolytic enzymes and sphingolipids in driving lateral segregation of phase domains thus determining long-range surface topography.

Protein-induced surface structuring in myelin membrane monolayers.

Monolayers prepared from myelin conserve all the compositional complexity of the natural membrane when spread at the air-water interface. They show a complex pressure-dependent surface pattern that, on compression, changes from the coexistence of two liquid phases to a viscous fractal phase embedded in a liquid phase. We dissected the role of major myelin protein components, myelin basic protein (MBP), and Folch-Lees proteolipid protein (PLP) as crucial factors determining the structural dynamics of the interface. By analyzing mixtures of a single protein with the myelin lipids we found that MBP and PLP have different surface pressure-dependent behaviors. MBP stabilizes the segregation of two liquid phases at low pressures and becomes excluded from the film under compression, remaining adjacent to the interface. PLP, on the contrary, organizes a fractal-like pattern at all surface pressures when included in a monolayer of the protein-free myelin lipids but it remains mixed in the MBP-induced liquid phase. The resultant surface topography and dynamics is regulated by combined near to equilibrium and out-of-equilibrium effects. PLP appears to act as a surface skeleton for the whole components whereas MBP couples the structuring to surface pressure-dependent extrusion and adsorption processes.