Free energies of molecular bound states in lipid bilayers: lethal concentrations of antimicrobial peptides.

Abstract:

: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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Huang HW

doi

10.1016/j.bpj.2009.01.030

subject

Has Abstract

pub_date

2009-04-22 00:00:00

pages

3263-72

issue

8

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(09)00505-0

journal_volume

96

pub_type

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