Fig. 2.

SAXS-based identification of pH-dependent mesophase transitions. (A) Ionizable lipid, chol, and buffer and (B) ionizable lipid, chol, buffer, and polyA. Data show the three ionizable lipids, MC3, KC2, and DD, for comparison. (C) Schematic representation of lipid phases with decreasing pH from top to bottom showing a trend from negative curvature toward zero curvature with increasing headgroup protonation: Inverse micellar fluid isotropic $L_{\mathit{II}}$ , inverse micellar cubic with P6₃/mmc symmetry, inverse micellar cubic with Fd3m symmetry, inverse hexagonal $H_{\mathit{II}}$ , and bicontinuous cubic Pn3m. In the presence of polyA (panel B), coexistence of lipid mesophases with a complexed, nucleic acid containing, phase is observed. In the pH range from 5.0 to 6.0 typically $H_{\mathit{II}}$ and $H_{\mathit{II}}^c$ coexist. See main text for further information.