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

Lipid nanodiscs (LNDs) provide versatile platforms for membrane protein research and function as innovative drug delivery systems. This study presents the structural characterization of LNDs composed of poloxamer 407 (PX407) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) using small-angle X-ray scattering (SAXS) analysis, further supported by turbidity assessment and transmission electron microscopy observation. Among the evaluated poloxamers, PX407, which contains the highest proportion of hydrophobic poly(propylene oxide) segment, exhibited superior DMPC solubilization capability. SAXS analysis, employing the core-shell bicelle-belt model, indicated that PX407-DMPC mixtures formed discoidal nanostructures. These structures preserved membrane thickness comparable to conventional phospholipid bilayers while achieving core diameters of 17-30 nm─over three times larger than those of styrene-maleic acid-based LNDs under similar conditions. The dimensions were systematically regulated by salt concentration and polymer-to-lipid ratio, with greater stability observed at higher polymer content (PX407: DMPC = 2:1 mass ratio) and elevated salt concentrations (≥300 mM NaCl). Although these LNDs appeared to be unstable above the DMPC gel-to-liquid crystalline phase transition temperature (∼24 °C), their larger size and temperature-responsive properties suggest potential applications in membrane protein research requiring extensive lipid platforms and in systems benefiting from temperature-dependent behavior.