Free energies of molecular bound states in lipid bilayers: lethal concentrations of antimicrobial peptides.
The lipid matrix, or the lipid bilayer, of cell membranes is a natural binding site for amphipathic molecules, including antimicrobial peptides, pore-forming proteins, and many drugs. The unique property of pore-forming antimicrobial peptides is that they exhibit a threshold concentration (called the lethal concentration or the minimum inhibitory concentration) for activity, below which no effect is seen. Without this property, antimicrobial peptides would not be effective self-defense weapons, because they would have harmed all cells at any concentration. The question is what gives rise to this unique property? This study provides a free energy description for the origin of a threshold concentration. The same free energy applied differently also explains the binding of drugs that shows no threshold concentrations. The idea is compared with theories of micellar solutions that require a large oligomer size (n 15) to achieve a threshold concentration. The elasticity of lipid bilayers makes the phenomena in membranes different. The majority of antimicrobial peptides have a large negative binding energy to the bilayer interface, but the binding causes an expansion in the membrane area, or equivalently a thinning in the membrane thickness. This elastic energy of membrane thinning elevates the energy level of interfacial binding with the peptide concentration, hence gives rise to a threshold concentration for forming pores containing as few as four peptides.
Huang
Huey W
HW
Department of Physics and Astronomy, Rice University, Houston, Texas 77251, USA.
D000408:Alamethicin / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D001516:Bees; D003474:Curcumin / Q000378:metabolism; D004548:Elasticity; D008051:Lipid Bilayers / Q000378:metabolism*; D008555:Melitten / Q000378:metabolism; D008958:Models, Molecular; D010713:Phosphatidylcholines / Q000378:metabolism; D013816:Thermodynamics
D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D008555:Melitten; D000408:Alamethicin; C017251:1,2-oleoylphosphatidylcholine; D003474:Curcumin