Comparing lipid packing between nanodiscs and native membranes

Hernandez, Luis M Real; Levental, Ilya

doi:10.1016/j.bpj.2021.11.333

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“…47 The authors attributed this to the smaller size of the nanodiscs compared to the pure DMPC vesicles and the presence of lipids that probably do not participate in the cooperative phase transition due to their interactions with the polymer and therefore their increased ordering compared with DMPC vesicles. 47,48 Similar to Bjørnestad et al, who recently reported that gel-like membranes more easily solubilize with SMA(3:1), we observe a seemingly more efficient solubilization at low temperatures. 23 This is not only true for SMA(2:1) but also for DIBMA.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Structural Insights into Polymer-Bounded Lipid Nanodiscs

et al. 2023

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Membrane proteins are an essential part of signaling and transport processes and are targeted by multiple drugs. To isolate and investigate them in their native state, polymer-bounded nanodiscs have become valuable tools. In this study, we investigate the lipid model system dimyristoyl-phosphocholine (DMPC) with the nanodisc-forming copolymers styrene maleic acid (SMA) and diisobutylene maleic acid (DIBMA). Using small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS), we studied the influence of polymer concentration and temperature on the nanodisc structure. In Tris buffer, the size of nanodiscs formed with SMA is smaller compared to DIBMA at the same polymer ratio. In both cases, the size decreases monotonically with increasing polymer concentration, and this effect is more pronounced when using SMA. Measurements at temperatures (T) between 5 and 30 °C in phosphate buffer showed an incomplete solubilization at high T even at polymer/lipid ratios above that required for complete lipid solubilization. For DIBMA, the nanodiscs developed at lower temperatures are stable and the net repulsion increases, while for SMA, the individual nanodiscs possess smaller sizes and are less affected by T. However, using DLS, one can observe SMA agglomerates at low T. Interestingly, for both polymers, no drastic changes of the observable parameters (radius and bilayer thickness) are seen upon cooling, which would indicate a sharp (first-order) phase transition from liquid-crystalline to gel, but only gradual changes. Hence, we conclude that the transition from a gel toward a liquid-crystalline lipid phase proceeds over a broad T-range compared to a continuous lipid bilayer. These results can pave the way toward the development of better protocols for studying membrane proteins stabilized in this type of membrane mimics.

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Section: ■ Results and Discussionmentioning

confidence: 99%