Fluorescence Probe Study of Bicelle Structure as a Function of Temperature:  Developing a Practical Bicelle Structure Model

Abstract

Bilayered mixed micelles or bicelles are magnetically anisotropic, self-assembling model membrane structures comprised of long-chain phospholipids and short-chain detergent molecules. In the most widely accepted model of this system, the bicelle is discoid in shape, with the short-chain DHPC molecules aggregating to form rims around long-chain DMPC bilayers. While this model is consistent with most NMR and scattering data (X-ray and neutron), it inadequately describes the liquid-crystalline behavior of bicelle solutions at temperatures where magnetic alignment occurs. Temperature plays a central role in the structure of lipid aggregates, and the impact of temperature on bicelles has not been studied as extensively as composition and concentration. Therefore, a series of fluorescence probe and resonance energy transfer (FRET) measurements of labeled bicelle solutions as a function of temperature were conducted to monitor lipid mixing as an indication of bicelle structure and aggregation. The results of these measurements are not consistent with the large-scale changes in lipid mixing with temperature that have been attributed to bicelle solutions in other studies. The spectral data indicate that there is reorganization within mixed lipid aggregates as a function of temperature and bilayer fusion. In an attempt to reconcile these data with physical data and the theory of liquid-crystalline behavior, the authors speculate that the structure of bicelles is an interconnected network of DMPC bilayers interrupted by DHPC rimmed pores at elevated temperatures.

Bicelles as model membranes for solid‐ and solution‐state NMR studies of membrane peptides and proteins

“…A disk fusion would be necessary to reach an appropriate size for cooperative alignment (43). Moreover, this model does not reconcile with the increase of viscosity (vide supra) occurring at the temperature at which orientation begins and which suggests the formation of large aggregates (74). According to the results published by several research groups using diverse techniques such as small angle X-ray scattering (SAXS), 31 (77), small-angle neutron scattering (SANS) (56, 78 -80), and fluorescence probe and resonance transfer (FRET) (74), it appears that different oriented and isotropic lipid organizations exist depending on the temperature, lipid concentration, and DMPC/DHPC (q) ratio.…”

“…According to the results published by several research groups using diverse techniques such as small angle X-ray scattering (SAXS), 31 (77), small-angle neutron scattering (SANS) (56, 78 -80), and fluorescence probe and resonance transfer (FRET) (74), it appears that different oriented and isotropic lipid organizations exist depending on the temperature, lipid concentration, and DMPC/DHPC (q) ratio. In addition, FRET (74) and SANS experiments (56,78), along with tracer diffusion measurements performed by NMR (37), have suggested that oriented bicelles would not adopt a discoidal shape, but undergo edgeto-edge contacts, and this is equivalent to DMPC lamellae perforated by DHPC-stabilized pores (37). This model, also known as the Swiss cheese model (31), is presented in Fig.…”

NMR in soft materials: A study of DMPC/DHPC bicellar system

“…in the gel phase, the size of bicelles is small and they are free to perform unrestricted isotropic tumbling [37]. For higher lipids concentration and higher q values the perforated lamellae morphology is also considered [38]. Assuming the bicelle's radius 5.6 nm, determined from our SAXS experiment, the Stokes-Einstein equation yields a ''whole bicelle'' diffusion coefficient of 4.4 10 À11 m 2 /s assuming a water like viscosity.…”

When detergent meets bilayer: Birth and coming of age of lipid bicelles

“…The high diffusion rate measured for tetramethylsilane (TMS) in oriented bicelles would require extensive transient edge-to-edge contacts in the disk model [156]. Measurements of high viscosity in orientable bicelles [157,158] contradict the theory of individual disks and suggest some entangling. The use of optical microscopy and SANS found yet another bicelle morphology, described as “wormlike micelles” and depicted in Fig.…”