Combining MAS and oriented solid-state NMR of membrane-associated antimicrobial peptides

I will present solid-state NMR investigations that provide in-depth insight into how antimicrobial peptides selectively permeabilize bacterial membranes. The studies reveal peptide-lipid interactions, peptide topology, penetration depth, oligomerization and dynamics. These structural investigations have changed our view how antimicrobial peptides insert and interact with membranes and new concepts for designing new antimicrobial drugs and polymers have emerged. Clearly, both the peptides and the lipids are highly dynamic, change and mutually adapt their conformation, membrane penetration and detailed morphology on a local and a global level. As a consequence, the peptides and lipids can form a wide variety of supramolecular assemblies in which the more hydrophobic sequences preferentially adopt transmembrane alignments and have the potential to form oligomeric structures. In contrast, charged amphipathic sequences tend to stay intercalated at the membrane interface. Although the membranes are soft and can adapt, at increasing peptide density they cause pronounced disruptions of the phospholipid fatty acyl packing. At increasing local or global concentrations the peptides result in transient membrane openings, rupture and ultimately lysis.

The studies also show the importance of lipid composition and sample composition, which requires adaptation of the NMR techniques and the equipment used. Both MAS and oriented solid-state NMR provide highly complementary information.

Bibliography

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2. Saad, A., Raya, J., Bechinger, B., Structure and dynamics of the magainin 2 antimicrobial peptide in biomimetic lipid bilayers by solid-state NMR, Biochemistry, 64, 4296-4308 (2025)

3. Saad, A. and Bechinger, B., Solid-state NMR spectroscopy for structural studies of polypeptides in extended physiological membranes, Biochimica et Biophysica Acta – Biomembranes, 1866, 184162, (2024)