Docosahexaenoic acid alters bilayer elastic properties

Abstract

At low micromolar concentrations, polyunsaturated fatty acids (PUFAs) alter the function of many membrane proteins. PUFAs exert their effects on unrelated proteins at similar concentrations, suggesting a common mode of action. Because lipid bilayers serve as the common ''solvent'' for membrane proteins, the common mechanism could be that PUFAs adsorb to the bilayer/solution interface to promote a negative-going change in lipid intrinsic curvature and, like other reversibly adsorbing amphiphiles, increase bilayer elasticity. PUFA adsorption thus would alter the bilayer deformation energy associated with protein conformational changes involving the protein/bilayer boundary, which would alter protein function. To explore the feasibility of such a mechanism, we used gramicidin (gA) analogues of different lengths together with bilayers of different thicknesses to assess whether docosahexaenoic acid (DHA) could exert its effects through a bilayer-mediated mechanism. Indeed, DHA increases gA channel appearance rates and lifetimes and decreases the free energy of channel formation. The appearance rate and lifetime changes increase with increasing channel-bilayer hydrophobic mismatch and are not related to differing DHA bilayer absorption coefficients. DHA thus alters bilayer elastic properties, not just lipid intrinsic curvature; the elasticity changes are important for DHA's bilayer-modifying actions. Oleic acid (OA), which has little effect on membrane protein function, exerts no such effects despite OA's adsorption coefficient being an order of magnitude greater than DHA's. These results suggest that DHA (and other PUFAs) may modulate membrane protein function by bilayer-mediated mechanisms that do not involve specific protein binding but rather changes in bilayer material properties.bilayer material properties ͉ bilayer stiffness ͉ gramicidin channels ͉ hydrophobic mismatch ͉ polyunsaturated fatty acid

Amphiphile regulation of ion channel function by changes in the bilayer spring constant

“…3C, we find that d 0 ∼ 4.0 nm for bilayers formed using either DPhPC or DOPC. For comparison, the bilayer thickness at an applied potential of 200 mV, as estimated from capacitance measurements (assuming a dielectric constant of 2), is ∼4.2 nm for DPhPC∕n decane (21) and between 3.7-4.3 nm for DOPC∕n decane (24,25). The agreement between the measured bilayer thickness and the prediction based on Eq.…”

“…The gA analogues and amphiphile were added to both sides of the bilayer. Survivor plots of channel lifetimes were fitted by a single exponential distribution, NðtÞ∕Nð0Þ ¼ expf−t∕τg, where NðtÞ is the number of channels with duration longer than time t, and τ is the average lifetime (12,22,(24)(25)(26)(27)(28).…”

Eicosapentaenoic Acid Plays a Beneficial Role in Membrane Organization and Cell Division of a Cold-Adapted Bacterium,Shewanella livingstonensisAc10

“…The membranes at the mid-cell regions in dividing cells form a highly curved structure. Although the bending rigidity of PUFA-containing bilayers is generally low, the presence of highly curved intracellular vesicles suggests that deficiency in EPA did not impair the membrane curvature in general (8). Our results, rather, suggest that EPA was required for the precise localization of a curvaturegenerating mechanism at low temperatures.…”

Axonal Gradient of Arachidonic Acid-containing Phosphatidylcholine and Its Dependence on Actin Dynamics

“…This idea is consistent with the previous report that the axon membrane exhibits a gradient from a lower membrane tension at the growth cone to a higher membrane tension at the cell body (27). Further, high localization of LCPUFAs, which can be released from LCPUFA-PCs, on the distal axon might affect membrane protein function by changing bilayer elasticity (28).…”