Lipid-based nanodiscs as models for studying mesoscale coalescence – a transport limited case

Abstract

Lipid-based nanodiscs (bicelles) are able to form in mixtures of long- and short-chain lipids. Initially, they are of uniform size but grow upon dilution. Previously, nanodisc growth kinetics have been studied using time-resolved small angle neutron scattering (SANS), a technique which is not well suited for probing their change in size immediately after dilution. To address this, we have used dynamic light scattering (DLS), a technique which permits the collection of useful data in a short span of time after dilution of the system. The DLS data indicate that the negatively charged lipids in nanodiscs play a significant role in disc stability and growth. Specifically, the charged lipids are most likely drawn out from the nanodiscs into solution, thereby reducing interparticle repulsion and enabling the discs to grow. We describe a population balance model, which takes into account Coulombic interactions and adequately predicts the initial growth of nanodiscs with a single parameter - i.e., surface potential. The results presented here strongly support the notion that the disc coalescence rate strongly depends on nanoparticle charge density. The present system containing low-polydispersity lipid nanodiscs serves as a good model for understanding how charged discoidal micelles coalesce.

Supported Lipid Bilayer Formation from Phospholipid-Fatty Acid Bicellar Mixtures

“…One promising method involves the deposition of bicelles, which are typically viewed as disk-like nanostructured assemblies composed of long-chain and short-chain phospholipid (or detergent) molecules that are concentrated in the middle bilayer and edge regions, respectively. , In actuality, the specific morphology of bicellar mixtures, which are sometimes referred to as bilayered mixed micelles , or nanodiscs, can encompass disk-like structures as well as other types of nanostructured assemblies, such as worm-like micelles and perforated sheets, depending on factors such as the q -ratio (molar ratio of long- to short-chain phospholipids), total lipid concentration, lipid composition, and temperature. − While bicelles were originally developed as suitable membrane environments to host transmembrane proteins for structural biology studies, ,− they have also proven to be useful tools for SLB fabrication, including simplified ones containing zwitterionic phospholipids − as well as more complex ones that include various fractions of charged phospholipids , or cholesterol, and are also useful for micropatterning applications . One key advantage of bicelles is that they are easier to prepare than conventionally used vesicles, and the main processing steps involve freeze–thaw–vortex cycling without the need for strict size control. , Mechanistically, SLB formation involves bicelle adsorption and fusion on a solid support whereby long-chain phospholipids self-assemble into a conformal SLB while short-chain phospholipids return to the bulk phase .…”

Versatile formation of supported lipid bilayers from bicellar mixtures of phospholipids and capric acid

“…Bicelles are an important class of membrane-mimicking lipid nanostructures that self-assemble from mixtures of long- and short-chain phospholipids under appropriate processing conditions 1 , 2 . Also known as lipid nanodisks 3 or bilayered mixed micelles 4 , 5 , bicelles can exist in a wide range of morphologies (e.g., perforated sheets and wormlike micelles) depending on parameters such as temperature, q-ratio (long- to short-chain phospholipid molar ratio), total lipid concentration, and lipid composition, and are widely conceptualized as two-dimensional disks whereby long-chain phospholipids constitute a planar lipid bilayer surface and the short-chain phospholipids form a rimmed edge around the bilayer 6 – 12 . Since they can exhibit magnetic alignment in some cases, bicellar disks have long been used in the nuclear magnetic resonance spectroscopy field as membrane protein hosts 4 , 13 – 16 .…”

Morphology-Induced Defects Enhance Lipid Transfer Rates

“…13 The long-chain lipids constitute the planar bilayer disk, while the short-chain lipids are sequestered at the disk's rim. Although the structural properties of bicellar mixtures have been extensively stud-ied, 14−18 their kinetic properties (i.e., stability 19 and lipid transfer rates 20 ) have not attracted much attention. Molecular transfer kinetics have been shown to affect the formation of polymeric, surfactant and lipid-based micelles, and their stabilities.…”

“…The long-chain lipids constitute the planar bilayer disk, while the short-chain lipids are sequestered at the disk's rim. Although the structural properties of bicellar mixtures have been extensively studied, − their kinetic properties (i.e., stability and lipid transfer rates) have not attracted much attention. Molecular transfer kinetics have been shown to affect the formation of polymeric, surfactant and lipid-based micelles, and their stabilities. − We recently reported a 150-fold enhancement in the interparticle lipid transfer rate constant, k inter , of dimyristoyl-PC (DMPC) bicelles (0.156 ± 0.011 h –1 ) compared to that of DMPC ULVs [(1.01 ± 0.06) × 10 –3 h –1 ].…”