Morphology and interaction between lipid domains

Abstract

Cellular membranes are a heterogeneous mix of lipids, proteins and small molecules. Special groupings enriched in saturated lipids and cholesterol form liquid-ordered domains, known as "lipid rafts," thought to serve as platforms for signaling, trafficking and material transport throughout the secretory pathway. Questions remain as to how the cell maintains small fluid lipid domains, through time, on a length scale consistent with the fact that no large-scale phase separation is observed. Motivated by these examples, we have utilized a combination of mechanical modeling and in vitro experiments to show that membrane morphology plays a key role in maintaining small domain sizes and organizing domains in a model membrane. We demonstrate that lipid domains can adopt a flat or dimpled morphology, where the latter facilitates a repulsive interaction that slows coalescence and helps regulate domain size and tends to laterally organize domains in the membrane.bilayer mechanics | lipid rafts | membrane morphology T he plasma and organelle membranes of cells are composed of a host of different lipids, lipophilic molecules, and membrane proteins (1). Together, they form a heterogeneous layer capable of regulating the flow of materials and signals into and out of the cell. Lipid structure and sterol content play a key role in bilayer organization, where steric interactions and energetically costly mismatch of lipid hydrophobic thickness result in a line tension that induces lateral phase separation (2). Saturated lipids and cholesterol are sequestered into liquid-ordered (L o ) domains, often known as "lipid rafts," distinct from an unsaturated liquid-disordered (L d ) phase (3-5). Domains whose lipids include saturated sphingolipids and cholesterol, with sizes in the range of ≈50-500 nm, have been implicated in a range of biological processes from lateral protein organization and virus uptake to signaling and plasma-membrane tension regulation (6-18). In the biological setting, maintenance of small domain size is thought to arise from a combination of lipid recycling and energetic barriers to domain coalescence (19)(20)(21) [potentially provided by transmembrane proteins (22)], ostensibly resulting in a stable distribution of domain sizes. These biological examples serve as a motivation to better understand the biophysical mechanisms that maintain small lipid domains over time and pose challenges to the classical theories of phase-separation and "domain ripening" [such as Cahn-Hilliard kinetics (23)].A simple physical model that describes the evolution of lipid domain size and position predicts that domains diffuse and coalesce, such that the number of domains constantly decreases, whereas the average domain size constantly increases (23). Indeed, models of 2D phase separation have been studied in detail for many physical systems (24-27), and where the phase boundary is unfavorable and characterized by an energy per unit length (28), the domain size grows continuously (23,29,30). However, membranes can adopt 3D morphologi...

Competition between line tension and curvature stabilizes modulated phase patterns on the surface of giant unilamellar vesicles: A simulation study

“…This caused non-equilibrium stabilization of multiple small domains. Kinetic trapping of domains by curvature is an experimentally observed phenomenon [28], but we are interested in studying equilibrium configurations.…”

Molecular mechanisms in signal transduction at the membrane

“…Bending of membranes creates a mechanism for long-range lateral force transmittance, even though the membrane itself is liquid. Consequences of this include the exotic stripe and hexagonal patterns of domains that form in phase-separated membranes 23,36,[44][45][46] as well as protein-protein interactions and possibly regulation 39,47,48 . An important corollary of these observations is that forcibly bending membranes necessarily imposes differential forces on structures in the membrane.…”

Multidomain and ground state configurations of two-phase vesicles

“…A significant part of the relevant literature focuses on studying microdomains from a non-equilibrium perspective, addressing issues such as growth dynamics and the recycling mechanism [7][8][9][10][11]. Numerous studies have also been devoted to understanding equilibrium configurations of multiphase vesicles [6,10,[12][13][14][15][16][17][18][19][20][21][22][23]. For recent reviews, see [24,25].…”