Abstract

Antimicrobial and toxin peptides spontaneously induce pores in cell membranes. Experiments showed that these are cooperative phenomena that exhibit a non-linear concentration dependence characterized by a threshold and a rapid rise to saturation as the concentration exceeds the threshold. The lecture consists of the following topics

1) Introduction—biology of antimicrobial peptides and potential applications (drug, gene/drug delivery, nanotechnology).

2) The structural basis of the pore-making mechanism. Experiments showed that peptide binding to lipid bilayers creates two distinct states depending on the bound-peptide to lipid ratio P/L. For P/L below a threshold P/L*, all of the peptide molecules are in the S state that has the following characteristics: (1) there are no pores in the membrane, (2) the axes of helical peptides are oriented parallel to the plane of membrane, and (3) the peptide causes membrane thinning in proportion to P/L. As P/L increases above P/L*, essentially all of the excessive peptide molecules occupy the I state that has the following characteristics: (1) transmembrane pores are detected in the membrane, (2) the axes of helical peptides are perpendicular to the plane of membrane, (3) the membrane thickness remains constant for P/L > P/L*.

3) Physics of peptide-membrane interactions. Theory of membrane elasticity. A molecular model of peptide-membrane interaction. Thermodynamics of pore formation induced by peptides. Why are the peptide-induced pores stable?