Membrane lipid bilayers curvature stress

A different type of curvature in bilayers can also result from the unequal distribution of lipids between the two monolayers, with one mono-layer having more lipid molecules than the other. This curvature is different from the curvature stress described above in that it originates from the total number of lipids on each side of the membrane and not from an inherent curvature in each lipid molecule. This curvature could be important in the budding of lipid vesicles (Huttner and Zimmerberg, 2001) and would be expected to influence and be influenced by the curvature stress described above. 

The entire thermodynamic system of the membrane and TM protein must be considered to understand how the protein and bilayer achieve their native state. We have summarized four of the mechanisms, hydrophobic matching, tilt angles, and specific protein/lipid and protein/protein interactions that are important in determining the stability (Fig. 5). Other important factors, such as the stability of lipid/lipid interactions, have been left out of our protein-centric view. We describe a hydrophobic mismatch as an unfavorable interaction that can be relieved by the other three processes, but we would expect all these properties of the system to interact. We could easily describe the same equilibria by saying that a strain in curvature is relieved by a hydrophobic mismatch or that strong protein/protein packing interactions might help relieve the hydrophobic mismatch or curvature stress. The complex interplay between all these interactions is at the heart of what determines membrane protein stability and will no doubt be difficult to quantify. 

A biologic reason for the abundance of nonlamellar lipids in membranes is that they possess the ability to modulate the activities of membrane proteins (15, 16). It has been recognized that membranes exist in a state of curvature frustration, which may be sufficiently large to have significant effect on certain protein conformations (17). Many examples show that the lipid bilayer elastic curvature stress indeed couples to conformational changes of membrane proteins (15, 18, 19). Protein kinase C is one such example of an enzyme activated by lipids that exhibit a propensity for nonlamellar phase formation (20). The activity of Ca " -ATPase from sarcoplasmic reticulum membranes also strongly correlates with the occurrence of nonbilayer lipids in the membrane and increases with the increase of their amount. It is noteworthy that the protein activity does not depend on the chemical structure of the lipids but only on their phase propensity thus specific binding interactions are ruled out. The list of proteins with activities that depend on the phase properties... 

The release profiles suggest that the lysoPPC and PA hydrolysis products, which are formed in a 1 1 molar ratio by SPLA2, are incorporated into the target membranes [51], leading to the increase in the permeability of the target liposomal membranes. These hydrolysis products, due to their non-bilayer forming molecular shapes, induce a curvature stress [52, 53] and/or form small-scale lipid domains [33, 36], which lead to membrane defects and consequently increased membrane... 

Fig. 24. a) Schematic illustration of the "stretching" of water channel junctions during the continuous transformation between the D and G cubic phases, which occur with no disruption of the bilayer topology. A junction of four water channels in the Qu° phase is converted into two three-way junctions in the Qu° phase, b) Possible mechanism of membrane fusion the monolayers of two apposed lipid bilayers mix to form a stalk intermediate that expands radially to a trans monolayer contact (TMC), leading to rupture as a result of curvature and interstitial stresses and finally to the formation of a fusion pore. 

The purpose of this chapter is to summarize some recent developments in the physics of lipid bilayers that demonstrate the existence of curvature-elastic stresses in bilayers and to review mechanisms whereby the resultant forces may couple to membrane protein conformations (see also references 1-3 for reviews). A consequence of these forces is that membrane proteins may have mechanistic themes that are qualitatively different from themes operative in aqueous proteins. Moreover, because these forces are directed generally parallel to the membrane surface, the actual conformational motions to which the forces couple may ultimately be simpler to understand than the complex conformations of aqueous proteins. 

When membranes fuse, the so-called stalk hypothesis suggests that the intermediate hemifusion state (Fig. 6.4c) comprises a structure in which proximal monolayers layers are connected by a bent stalk and the distal layers are pulled towards each other, thus forming a dimple (see also Fig. 6.5) The stalk model has been supported by theoretical and experimental observations. The fusion of model membranes appears to occur via the same series of fusion intermediates as those in vivo, although the approach of membranes is not Rab/SNARE mediated but is driven by reduced bilayer repulsion forces arising from hydration, electrostatic interactions, thermal fluctuations (Helfrich interaction) or osmotic stress. Membrane fusion is also promoted by defects introduced into the membrane by lateral phase separation (for example of lipid rafts, see above), high spontaneous membrane curvature, or addition of macromolecules or proteins into the membrane. 

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