Domain-driven morphogenesis of cellular membranes

Abstract

Cellular membrane systems delimit and organize the intracellular space. Most of the morphological rearrangements in cells involve the coordinated remodeling of the lipid bilayer, the core of the membranes. This process is generally thought to be initiated and coordinated by specialized protein machineries. Nevertheless, it has become increasingly evident that the most essential part of the geometric information and energy required for membrane remodeling is supplied via the cooperative and synergistic action of proteins and lipids, as cellular shapes are constructed using the intrinsic dynamics, plasticity and self-organizing capabilities provided by the lipid bilayer. Here, we analyze the essential role of proteo-lipid membrane domains in conducting and coordinating morphological remodeling in cells.

Figure 1

Common tubulo-vesicular patterns of membrane shape in cellular and reconstituted systems. A. Large lipid vesicle spontaneously self-assembled upon hydration of a dried lipid film; B. Deformation of lipid vesicles produced by I-BAR proteins (from [96]). C. Deformation of lipid vesicles induced by COP I assembly (from [97]). D. Snapshot of membrane morphology of endoplasmic reticulum (from [98]). All bars 200 nm.

Figure 2

Schematic pathway of the MOD emergence. Creation of curved areas in the membrane, here due to thermal undulations, is coupled to the lateral redistribution of the membrane components according to their curvature preferences and to the curvature-driven binding of proteins. This coupling first leads to the enhancement of the undulations, then to the MOD emergence, if more components stabilizing membrane curvature (blue banana) or clustering on the MOD membrane (blue caps) are added. MODs can quickly disappear if the curvature-active components leaves, e.g. via desorption and disassembly coupled to GTP or ATP hydrolysis.

Figure 3

Basic shapes of MOD. A. Principal curvature of a surface, K_1,2=1/R_1,2 ; B. MOD shapes, spherical, cylindrical and saddle-like, corresponding to different sets of principal curvatures indicated; C. Protein polymerization patterns corresponding to simple MOD geometries shown in B; the images illustrate interaction patterns leading to stabilization of a protein scaffolding in space.

Figure 4

Evolution of MOD. Similar cap-like precursors can develop into tubular or spherical MODs dependently on the MOD composition and forces acting on the MOD. Elongated proteins or membrane-binding protein domains, such as BAR [refs], situated along one of the principle directions on the membrane surface (see Figure 3) lead to cylindrical MOD, while more round-like proteins, e.g. clathrin triskelia, do not distinguish the principal directions leading to spherical MOD. Evolution of the spherical MOD inevitably leads to the appearance of the new MOD, the neck. For fluid-like domains, the neck formation is promoted by the line tension on the MOD edge (red ring): the line tension enforce the lessening of the edge leading to the closure of the spherical MOD. The length of the neck MOD (L) is proportional to its radius (R), this proportionality defines the evolution of this MOD towards thin and short membrane neck, an established intermediate in fusion and fission reactions.