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Membrane Lipid Biology

Cell membranes constitute one of the fundamental structural and functional elements of living organisms. These complex mixtures of lipids and proteins form the outer boundary of the cell. They distinguish between the ‘inside" and the "outside", and allow the cell to communicate with its environment and keep its integrity. While covalent bonds between the atoms in the protein and lipid molecules determine their structural integrity, their macromolecular aggregate that forms the actual membrane retains its association without the benefit of covalent bonds, and is governed largely by the "hydrophobic effect". This force is in turn is based on the unique properties of

water. While water has great solvent power for polar substances such as ions, it lacks solubility for non-polar substances. Amphipathic molecules, which contain both polar and non-polar regions, accommodate in a water environment by maximizing the interaction of the polar parts of the molecules with the aqueous phase andshield the interaction of the non-polar region from water.

Phospholipid Structure
Phospholipids are the major lipid building blocks of mammalian membranes. Their molecular structure consists of a polar headgroup, attached to a backbone (glycerol for glycerophospholipids, ceramide for sphyngolipids), to which fatty acylgroups are attached with carbon chains of typically 16 to 22 carbon atoms long, with 0 to 6 double bonds.

Often a happy solution for phospholipids is a double layer with the hydrocarbon chains sequestered away from the water in the interior of the bilayer , while the polar phospholipid head groups maintain contact with the aqueous phase. Similarly, protein amino acid regions with hydrophobic side chains sequester away from water while polar amino acid side chains are exposed to the aqueous phase.

The lipid-lipid and lipid-protein interactions in membranes, determined by these forces are extremely important for the function of the membrane. Consequently research on membrane structure has become an important subject at the most basic level of the discipline of cell biology.

Membrane bilayer
Phospholipids form bilayers driven by the hydrophobic effect

In recent years, it has been recognized that the role of the lipid membrane bilayer is far from the rather anonymous, passive and structure less embedding solvent for membrane proteins as depicted in most general textbooks. In that view, the lipid bilayer is a thin two-dimensional bimolecular sheet, has no particular transverse or lateral structure or dynamics and no coupling to the proteins. The otherwise successful paradigm of the Singer/Nicolson fluid-mosaic model of bio-membranes may be in part responsible. This model seems to imply that the lipid-bilayer component of cell membranes is a structure-less fluid characterized by disorder and randomness rather than by molecular order and structure. In contrast however, lipid bilayers display order and structure, be it in a different sense than used in connection with the static structure of macromolecules. Lipid membranes are highly dynamic structured and complex fluids. They sustain fluctuations, cooperatively, and correlated dynamical modes that lead to local order out of disorder, properties important for membrane function. Membrane proteins are embedded in a lipid bilayer which accommodates by deformation to make a hydrophobic match. Amino-acids will interact with specific acyl-chains in the hydrophobic core, and the charged lipid head-groups interact with more hydrophilic amino acids at the water membrane interface.

Complex lipid/protein mixture at the plasma membrane

Lipids and proteins form complex mixtures at the plasma membrane, the outer boundary of the cell. The mixture distinguishes between ‘inside" and "outside", allowing the cell to communicate with its environment and keep its integrity. A change in protein conformation will be accommodated by a local change in lipid organization.

In addition to forming simple bilayers, lipids can organize in non-lamellar structures that affect the function of membrane proteins and can also segregate in local domains in the membrane. One example are the formation of sphingolipid-cholesterol domains, or rafts, that have a function in the sorting and transport of lipids and proteins as well as in signal transduction. Taken together, composition and organization of phospholipids in plasma membranes are essential to the integrity of the cell.

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