Lipid shape is a key factor for membrane interactions of amphipathic helical peptides

► Amphipathic peptides in membranes change their alignment from surface-bound to tilted. ► The re-alignment of the antimicrobial peptide MSI-103 is compared in many different lipids. ► The accurate 2H-NMR data allows for the first time a systematic generalization. ► In lipids with negative spontaneous curvature the peptide always remains surface-bound. ► Only a positive lipid curvature allows the peptide to tilt deeper into the membrane.