The role of polyunsaturated lipids in membrane raft function

Abstract

Docosahexaenoic acid (DHA), with 22 carbons and six double bonds, is the longest, most unsaturated fatty acid commonly found in humans. It represents the extreme example of an omega-3 (n-3) polyunsaturated fatty acid. Since early epidemiology studies, DHA has been linked to alleviation of an enormous number of human afflictions, including heart disease, cancer and neurological disorders. How one simple molecule can affect so many seemingly unrelated abnormalities has been a contentious question for many years. One research direction has investigated events that follow the uptake of DHA into animal cell plasma membrane phospholipids. Summarized here is a variety of membrane properties impacted by the incorporation of DHA. DHA’s dynamic shape, consisting of multiple configurations, is very different from what its static, stick structure would indicate. DHA-containing phospholipids have a wide hydrophobic base compared with their hydrophilic head and so induce nega tive curvature strain that severely impacts the activity of a variety of important membrane proteins. The unusual structure means that DHA-rich membranes are also surprisingly thin and support high permeability, compression, fusion and flip-flop rates. DHA does not exist in an environment that is independent from other membrane lipids. Of particular interest is the interaction of DHA-containing phospholipids with the major lipid raft components cholesterol and sphingomyelin. From a wide variety of biophysical studies, primarily done on model lipid monolayers and bilayers, a new hypothesis is proposed suggesting that DHA may alter plasma membrane lipid raft structure and hence essential cell signaling events. A fundamental role for DHA affecting a feature common to all cells, membrane structure and function, may explain its wide variety of reputed health benefits. Keywords: docosahexaenoic acid; lipid rafts; membrane structure; polyunsaturated fatty acids; n-3