Hybrid and Nonhybrid Lipids Exert Common Effects on Membrane Raft Size and Morphology

Abstract

Cell membranes perform multiple functions that may be facilitated by the lateral organization of lipids and proteins into nanoscale compartments, termed membrane rafts. Understanding the origins of raft domains and the physicochemical mechanisms that control their finite small size is important for elucidating their functional significance and manipulating their properties. However, it has proven difficult to characterize rafts in cells due to the chemical complexity of biological membranes, and various models have been advanced based on theory and experiments of representative model membranes. In one popular model, a special role in the domains existence and properties has been postulated for chain-asymmetric or hybrid lipids having a saturated sn-1 chain and an unsaturated sn-2 chain. It was proposed that these lipids align in a preferred orientation at the boundary of ordered and disordered phases, lowering the interfacial energy and thus reducing domain size. Such a unique "line-active" role for hybrid lipids is an appealing explanation for nanoscopic rafts, as animal cell membranes contain few symmetric low-melting lipids but an abundance of hybrid lipids. We present data from small-angle neutron scattering and fluorescence techniques demonstrating the existence of nanoscopic and modulated liquid phase domains in a mixture composed entirely of nonhybrid lipids and cholesterol. Our results are indistinguishable from those obtained previously for mixtures containing hybrid lipids, conclusively showing that hybrid lipids are not required for the formation of nanoscopic liquid domains. These findings present new challenges for current theoretical descriptions of nanodomains.