Phospholipid Bilayer Nanodiscs: A Powerful Tool to Study the Structural Organization and Biochemical Reactivity of Proteins in Membrane-like Environments

Abstract

Nanodiscs are disc-like structures formed by two copies of a membrane scaffold protein, engineered from apolipoprotein A-I, surrounding a phospholipid mixture that can incorporate membrane proteins preserving their natural properties. They behave as soluble entities allowing the use of high-resolution structural techniques to determine the structural organization of the embedded membrane protein, and the use of solution biochemical-biophysical tools to measure its activity, assembly and interactions with other proteins in membranelike environments. In addition, nanodiscs are biocompatible which makes them an attractive technology to be used in therapy, drug discovery, and other biotechnological applications.

Enhanced imaging of lipid rich nanoparticles embedded in methylcellulose films for transmission electron microscopy using mixtures of heavy metals

“…Lipid rich nanoparticles (LRNPs) are of considerable importance in nanomedicine and basic research (see Hernández-Rocamora et al, 2014a; Poulos et al, 2015; Landreh and Robinson, 2015). An extensive range of LRNPs can be synthesized in the laboratory including liposomes, nanodiscs (Borch and Hamann, 2009) and bicelles (Poulos et al, 2015; Harroun et al, 2005; Rubio et al, 2011a; Vestergaard et al, 2015).…”

“…Liposomes have long been proposed as vehicles for drug and cosmetic delivery and have recently been standardized well enough for clinical trials to be performed (Sercombe et al, 2015). Nanodiscs and bicelles are more recent innovations and are commonly used as platforms for studies of membrane proteins (Borch and Hamann, 2009; Bayburt and Sligar, 2010; Hernández-Rocamora et al, 2014b; Schuler et al, 2016; Murakami, 2012; Ward et al, 2014), wherein direct binding of lipids to hydrophobic pockets of these systems has been shown to play a major role in their regulation (Pliotas et al, 2015; Pliotas and Naismith, 2016) and structural integrity (Tanaka et al, 2015). Naturally occurring lipid structures include enveloped viruses, multivesicular body-derived exosomes and lipoprotein particles.…”

Conformational Dynamics of Sensory Rhodopsin II in Nanolipoprotein and Styrene–Maleic Acid Lipid Particles

“…Currently, two membrane mimetic approaches, which provide monodisperse nanoparticles of ~ 10–15 nm diameter containing membrane proteins, are under development. In these approaches a protein‐lipid core is surrounded and stabilized either by an amphipathic protein belt, in the so‐called nanodiscs or nanolipoprotein particles (NLPs), or by a styrene–maleic acid (SMA) copolymer, yielding SMA‐lipid particles (SMALPs) . Both NLPs and SMALPs can be prepared from a variety of lipid mixtures and even native lipids of membrane extracts.…”

Phospholipid bilayer affinities and solvation characteristics by electrokinetic chromatography with a nanodisc pseudostationary phase

“…Nanodiscs are nanometer scale disc‐shaped phospholipid bilayer assemblies encircled by two genetically engineered belt or scaffold proteins (see Fig. ).…”