Poloxamer 407 and DMPC Form Large Lipid Nanodiscs: Structural Characterization Using Small-Angle X-ray Scattering

Area of Science:

• Biophysics
• Materials Science
• Nanotechnology

Background:

• Lipid nanodiscs (LNDs) are crucial for membrane protein studies and drug delivery.
• Poloxamers offer tunable properties for nanostructure formation.

Purpose of the Study:

• To structurally characterize LNDs formed by poloxamer 407 (PX407) and DMPC.
• To evaluate PX407's efficacy in DMPC solubilization and nanodisc formation.
• To explore the influence of salt concentration and polymer-to-lipid ratio on LND structure and stability.

Main Methods:

• Small-angle X-ray scattering (SAXS) with core-shell bicelle-belt modeling.
• Turbidity assessment.
• Transmission electron microscopy (TEM).

Main Results:

• PX407 demonstrated superior DMPC solubilization.
• PX407-DMPC mixtures formed discoidal nanostructures with diameters of 17-30 nm.
• Nanodisc dimensions and stability were tunable via salt concentration and polymer-to-lipid ratio.
• Higher stability was achieved at a 2:1 PX407:DMPC mass ratio and ≥300 mM NaCl.
• LNDs showed instability above DMPC's phase transition temperature (~24 °C).

Conclusions:

• PX407-DMPC LNDs are larger than traditional styrene-maleic acid LNDs.
• These LNDs possess tunable size and temperature-responsive characteristics.
• Potential applications include membrane protein research needing large lipid platforms and temperature-sensitive delivery systems.