Styrene/maleic acid (SMA) and related copolymers are attracting great interest because they solubilise membrane proteins and lipids to form polymer-encapsulated nanodiscs. These nanodiscs retain a lipid-bilayer core surrounded by a polymer rim and can harbour a membrane protein or a membrane-protein complex. SMA exists in different styrene/maleic acid molar ratios, which results in differences in hydrophobicity and solubilisation properties. We have recently demonstrated fast collisional lipid transfer among nanodiscs encapsulated by the relatively hydrophobic copolymer SMA(3:1). Here, we used time-resolved Förster resonance energy transfer to quantify the lipid-transfer kinetics among nanodiscs bounded by SMA(2:1), a less hydrophobic copolymer that is superior in terms of lipid and membrane-protein solubilisation. Moreover, we assessed the effects of ionic strength and, thereby, the role of Coulombic repulsion in the exchange of lipid molecules among these polyanionic nanodiscs. Collisional lipid transfer was slower among SMA(2:1) nanodiscs (kcol = 5.9 M-1 s-1) than among SMA(3:1) nanodiscs (kcol = 222 M-1 s-1) but still two to three orders of magnitude faster than diffusional lipid exchange among protein-encapsulated nanodiscs or vesicles. Increasing ionic strength accelerated lipid transfer in a manner predicted by the Davies equation, an empirical extension of the Debye-Hückel limiting law, or an extended equation taking into account the finite size of the nanodiscs. Using the latter approach, quantitative agreement between experiment and theory was achieved for an effective nanodisc charge number of z ≈ -33, which is an order of magnitude less than their nominal overall charge.
Keywords: Davies equation; Debye–Hückel theory; Lipid exchange; Polymer nanodiscs; SMALPs.