Effect of Line Tension on the Lateral Organization of Lipid Membranes

Abstract

The principles of organization and functioning of cellular membranes are currently not well understood. The raft hypothesis suggests the existence of domains or rafts in cell membranes, which behave as protein and lipid platforms. They have a functional role in important cellular processes, like protein sorting or cell signaling, among others. Theoretical work suggests that the interfacial energy at the domain edge, also known as line tension, is a key parameter determining the distribution of domain sizes, but there is little evidence of how line tension affects membrane organization. We have investigated the effects of the line tension on the formation and stability of liquid ordered domains in model lipid bilayers with raft-like composition by means of time-lapse confocal microscopy coupled to atomic force microscopy. We varied the hydrophobic mismatch between the two phases, and consequently the line tension, by modifying the thickness of the disordered phase with phosphatidylcholines of different acyl chain length. The temperature of domain formation, the dynamics of domain growth, and the distribution of domain sizes depend strongly on the thickness difference between the domains and the surrounding membrane, which is related to line tension. When considering line tension calculated from a theoretical model, our results revealed a linear increase of the temperature of domain formation and domain growth rate with line tension. Domain budding was also shown to depend on height mismatch. Our experiments contribute significantly to our knowledge of the physical-chemical parameters that control membrane organization. Importantly, the general trends observed can be extended to cellular membranes.Cellular membranes form closed volumes that define the cell and organelle identity, although ensuring the exchange of matter, energy, and information that is required for life. They do so by means of a complex protein and lipid composition that is actively regulated in time and varies not only among the different cellular membranes but also between the two leaflets that form the membrane bilayer (1). During the last years, it has also become clear that the existence of lateral heterogeneities or domains in membranes is essential for a number of cellular functions.The raft theory predicts the existence of lipid assemblies that are enriched in sphingolipids and cholesterol. These membrane domains are thought to behave as protein and lipid platforms, important for protein trafficking and sorting, cell signaling, and other cellular processes (2-4). Recent findings suggest that rafts are dynamic structures of transient nature and sizes in the nanometer range (5). Though still debated, the widely accepted view implies a situation far from equilibrium, where signaling or sorting processes would induce the coalescence of these lipid assemblies into more stable larger platforms in the membrane (6).However, the current knowledge of membrane organization is not sufficient to fully explain the behavior and functioning of cellular me...

Organization, dynamics, and segregation of Ras nanoclusters in membrane domains

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Clustering and Lateral Concentration of Raft Lipids by the MAL Protein

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Membrane raft association is a determinant of plasma membrane localization

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