The interaction of styrene maleic acid copolymers with phospholipids in Langmuir monolayers, vesicles and nanodiscs; a structural study.

Hypothesis: Self-assembly of amphipathic styrene maleic acid copolymers with phospholipids in aqueous solution results in the formation of 'nanodiscs' containing a planar segment of phospholipid bilayer encapsulated by a polymer belt. Recently, studies have reported that lipids rapidly exchange between both nanodiscs in solution and external sources of lipids. Outstanding questions remain regarding details of polymer-lipid interactions, factors influencing lipid exchange and structural effects of such exchange processes.

Adsorption of a styrene maleic acid (SMA) copolymer-stabilized phospholipid nanodisc on a solid-supported planar lipid bilayer.

Over recent years, there has been a rapid development of membrane-mimetic systems to encapsulate and stabilize planar segments of phospholipid bilayers in solution. One such system has been the use of amphipathic copolymers to solubilize lipid bilayers into nanodiscs. The attractiveness of this system, in part, stems from the capability of these polymers to solubilize membrane proteins directly from the host cell membrane.

An acid-compatible co-polymer for the solubilization of membranes and proteins into lipid bilayer-containing nanoparticles.

The fundamental importance of membrane proteins in drug discovery has meant that membrane mimetic systems for studying membrane proteins are of increasing interest. One such system has been the amphipathic, negatively charged poly(styrene-co-maleic acid) (SMA) polymer to form "SMA Lipid Particles" (SMALPs) which have been widely adopted to solubilize membrane proteins directly from the cell membrane. However, SMALPs are only soluble under basic conditions and precipitate in the presence of divalent cations required for many downstream applications.

Influence of Poly(styrene- co-maleic acid) Copolymer Structure on the Properties and Self-Assembly of SMALP Nanodiscs.

Polymer stabilized nanodiscs are self-assembled structures composed of a polymer belt that wraps around a segment of lipid bilayer, and as such are capable of encapsulating membrane proteins directly from the cell membrane. To date, most studies on these nanodiscs have used poly(styrene- co-maleic acid) (SMA) with the term SMA-lipid particles (SMALPs) coined to describe them. In this study, we have determined the physical and thermodynamic properties of such nanodiscs made with two different SMA copolymers.

Evidence of Lipid Exchange in Styrene Maleic Acid Lipid Particle (SMALP) Nanodisc Systems.

Styrene-alt-maleic acid lipid particles (SMALPs) are self-assembled discoidal structures composed of a polymer belt and a segment of lipid bilayer, which are capable of encapsulating membrane proteins directly from the cell membrane. Here we present evidence of the exchange of lipids between such "nanodiscs" and lipid monolayers adsorbed at either solid-liquid or air-liquid interfaces. This behavior has important implications for the potential uses of nanodiscs.