Perturbation of a lipid membrane by amphipathic peptides and its role in pore formation

Assaf Zemel, Avinoam Ben-Shaul*, Sylvio May

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


We study the structural and energetic consequences of (α-helical) amphipathic peptide adsorption onto a lipid membrane and the subsequent formation of a transmembrane peptide pore. Initially, each peptide binds to the membrane surface, with the hydrophobic face of its cylinder-like body inserted into the hydrocarbon core. Pore formation results from subsequent peptide crowding, oligomerization, and eventually reorientation along the membrane normal. We have theoretically analyzed three peptide-membrane association states: interfacially-adsorbed monomeric and dimeric peptides, and the multi-peptide transmembrane pore state. Our molecular-level model for the lipid bilayer is based on a combination of detailed chain packing theory and a phenomenological description of the headgroup region. We show that the membrane perturbation free energy depends critically on peptide orientation: in the transmembrane pore state the lipid perturbation energy, per peptide, is smaller than in the adsorbed state. This suggests that the gain in conformational freedom of the lipid chains is a central driving force for pore formation. We also find a weak, lipid-mediated, gain in membrane perturbation free energy upon dimerization of interfacially-adsorbed peptides. Although the results pertain mainly to weakly-charged peptides, they reveal general properties of the interaction of amphipathic peptides with lipid membranes.

Original languageAmerican English
Pages (from-to)230-242
Number of pages13
JournalEuropean Biophysics Journal
Issue number3
StatePublished - May 2005

Bibliographical note

Funding Information:
Acknowledgments A.Z. thanks the Yeshaya Horowitz Foundation for a doctoral fellowship. S.M. thanks the Thüringer Ministerium für Wissenschaft, Forschung und Kunst. The financial support of the Israel Science Foundation (grant 227/02) and the United States-Israel Binational Science Foundation (grant 2002-75) is gratefully acknowledged. The Fritz Haber Center is supported by the Minerva Foundation, Munich, Germany.


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