Sequence-dependent interactions between model peptides and lipid bilayers

Studying interaction between peptides and lipid membranes is helpful for understanding the working mechanism of amyloidogenic peptides and antimicrobial peptides, which are toxic to cells through disruption of the cell membrane. Although many efforts have been made to find out common mechanisms of the peptide-induced membrane disruption, detailed information on how the peptide's amino acid sequence affects its interaction with lipid bilayers is still lacking. In this study, three peptides termed as Pep11, P11-2, and QQ11, which share a similar backbone, were employed to explore how modifications on the peptide sequence as well as terminal groups influenced its interaction with the lipid membrane. Atomic force microscopy data revealed that the peptides could deposit on the membranes and induce defects with varied morphologies and stiffness. Fluorescence resonance energy transfer (FRET) experiments indicated that the introduction of the three peptides resulted in different FRET effects on either liquid or gel lipid membranes. DPH fluorescence anisotropy and Laurdan's generalized polarization analysis showed that P11-2 could insert into the lipid membrane and impact the lipid hydrophobic region while QQ11 influenced the order of the hydrophilic head of the lipid membrane. With these results, we have illustrated how these peptides interacted differently with the lipid membrane because of the modification of their sequences. Although these peptides did not relate to disease and antibiosis, we hope these results still could provide some clues for partly understanding the working mechanism of amyloidogenic peptides and antimicrobial peptides.