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Membrane Dynamics and Domains : Subcellular Biochemistry

During the past 30 or so years a great deal of information has accumulated on the composition of various cell membranes and how this is related to the dif ferent functions that membranes perform. Nevertheless, the task of explaining particular functions at the molecular level has been hampered by lack of struc tural detail at the atomic level. The reason for this is primarily the difficulty of crystallizing membrane proteins which require strategies that differ from those used to crystallize soluble proteins.

Front Matter Pages Janet M.

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Oliver, Janet R. Pfeiffer, Zurab Surviladze, Stanly L.

Activation of interfacial enzymes at membrane surfaces. - Semantic Scholar

Steinberg, Karin Leiderman, Margaret L. Sanders et al. Pages Bernd Wollscheid, Priska D. Lipid Composition of Membrane Domains. Kamen S.

The various functions of the lipid membranes are outlined in this schematic. Biological membranes are known to exist in different structures and phases, such as bilayers, micelles, hexagonal, and cubic phases [3]. However, the most common structure of membranes is described in the classic fluid mosaic model that was put forth by SJ Singer and GL Nicolson in [4]. According to this model, membranes are depicted as two-dimensional fluids made up of lipid bilayers that are interspersed with proteins in a mosaic-like fashion.

Flip-Flopping and Fluid Mosaic Model

The hydrophilic phosphate head groups of the lipid molecules are in contact with the aqueous environment at the outer surface of the bilayer, whereas the two hydrophobic lipid chains are sequestered to the inner side of the bilayer away from any contact with the fluidic environment. The fluid mosaic model incorporates the dynamic nature of bilayer membrane organization that occurs due to the constant rotational and lateral motion of the integral lipid and protein molecules.

Schematic showing the structure of a lipid bilayer membrane.

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The molecular composition of cell membranes is responsible for determining its physiochemical properties. For instance, a number of membrane properties including its phase behavior, viscosity ability to flow like a liquid , rigidity, and thickness are determined by the types of lipids and their densities found in the membrane [5]. Similarly, the accumulation of several curvature-sensing lipids and proteins tend to induce curvature in localized regions of the membrane that, at a larger scale, determines its shape [2].

Dynamic lipid-protein interactions on the cell membrane influences the distribution of these molecular components in the bilayer and results in the formation of distinct membrane domains, such as lipid rafts.

Such membrane domains serve as precursor sites for the formation of vesicles, invaginations, and protrusions that are essential for the transport of cellular cargo, as well as for internalization of pathogens. Furthermore, the lipids and proteins on the cell membrane diffuse freely within the bilayer unless they are tethered to cytoskeletal structures, extracellular matrix or to other membrane proteins. The continuous diffusion of molecular components within the bilayer, coupled to the loose packing of hydrocarbon tails of membrane lipids, is responsible for the viscous nature not solid-like nature of cell membranes [5].

Similarly, the rigid ring structures of cholesterol molecules inserted in between the phospholipids produces temperature-dependent effects on membrane structures. A diverse population of lipids, which mainly vary in size and chemical properties of their head groups and fatty acid chains, and the type of linkages formed between these two structural domains, constitute the cell membrane.


These include a number of phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, sphingolipids, phosphoinositides, glycolipids, and cholesterol [2]. While phosphatidylcholine and sphingolipids predominate the outer leaflet of the lipid bilayer, the inner leaflet is primarily constituted by phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine.

This chemical diversity is further magnified by the action of several membrane-bound enzymes that possess different lipid metabolizing functions. However, highly regulated pathways of lipid synthesis and transport across the cell influences the molecular composition of lipids in different cell organelles as well as within the different leaflets of the same bilayer that determines its physicochemical properties, and thus its biological functions [6].

Membrane lipids consist of phosphatidylcholine and sphingolipids on the outer leaflet, and phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine on the inner leaflet.

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Membrane dynamics during cellular wound repair

While lipids contribute primarily to the structural characteristics of cell membranes, an equally diverse set of proteins that localize to the membranes, including receptors, transporters, cell adhesion molecules, enzymes, and energy transducing proteins are involved in diverse biological functions associated with membranes. Proteins are recruited to membranes either through their interactions with membrane lipids or with other membrane proteins, and these interactions are closely regulated by post translational modifications of either of the interacting partners. At the membrane, proteins are either attached to a single leaflet of the lipid bilayer or they extend across the bilayer, in which case they are known as transmembrane proteins.

While some transmembrane proteins cross the membrane a single time single-pass transmembrane proteins , others pass in and out of the membrane several times multi-pass transmembrane proteins. In recent years, the structures of some membrane proteins have been identified through the use of techniques such as X-ray crystallography and NMR spectroscopy, but the structural characterization of the bulk of membrane proteins has been difficult due to the close association of these proteins with the lipid bilayer, where they are affected by membrane physicochemical properties [7] , [8] , The Cell: A Molecular Approach.

Any communication or interactions between the intracellular and extracellular spaces occurs through the plasma membrane, which forms the boundary between these two regions. One of its main roles at the interface is to serve as a permeability barrier that facilitates selective transport of ions and molecules in and out of the cell.

The hydrophobic core of the lipid bilayer serves as an impermeable layer for the water-soluble molecules, including ions and most biological molecules, to pass through.

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