Molecular basis for nanoscopic membrane curvature generation from quantum mechanical models and synthetic transporter sequences.

We investigate the physical origin of peptide-induced membrane curvature by contrasting differences between H-bonding interactions of prototypical cationic amino acids, arginine (Arg) and lysine (Lys), with phosphate groups of phospholipid heads using quantum mechanical (QM) calculations of a minimum model and test the results via synthetic oxaorbornene-based transporter sequences without the geometric constraints of polypeptide backbones. QM calculations suggest that although individual Lys can in principle coordinate two phosphates, they are not able to do so at small inter-Lys distances without drastic energetic penalties. In contrast, Arg can coordinate two phosphates down to less than 5 A, where guanidinium groups can stack “face to face”. In agreement with these observations, poly-Lys cannot generate the nanoscale positive curvature necessary for inducing negative Gaussian membrane curvature, in contrast to poly-Arg. Also consistent with QM calculations, polyguanidine-oxanorbornene homopolymers (PGO...