Antimicrobial peptides are small membrane active molecules of high toxicity. They constitute the first natural defense line against pathogens in animals and plants. During the last decade, thousands of these AMPs have been isolated from their natural sources or designed de novo with the goal of creating another generation of antibiotics to counter increasingly resistant bacteria. Hope is even that the synthesis of bio-mimetic artificial AMPs may lead to readily designed new drug systems of high affinity and efficiency also for the treatment of major diseases as cancer and neurodegenerative disorders.
One class of candidates was designed to mimic the lethal frog venom magainin by systematic variation of the amino acid sequence. The study presented did address the synthetic antimicrobial peptide, KLA1, and explored its effect on a lipid model bilayer by a combination of methods including cryo-TEM, conductivity experiments, micromechanical deformation studies by micropipette aspiration, and confocal microscopy. Experiments were done on small unilamellar vesicles (SUVs), planar membrane stacks, black lipid membranes (BLMs), and giant unilamellar vesicles (GUVs). The results to be presented and discussed focus on mechanisms to induce membrane lysis. More experiments intend to correlate the findings to functional structures, and their modification upon peptide interaction.
The results assembled indicate that the system represents, at low peptide concentrations, an example for a "living micro-sieve": the high membrane permeability found seems to be due to the spontaneous formation of transitory membrane holes. These pores must be of toroidal shape for energetic reasons so that their formation does not require a lot of curvature energy. Such pores are close to minimal energy conformations and may fluctuate. Their formation and stability is most probably governed by the interplay of diffusion limited reversal peptide aggregation. An aggregate may then act as a local defect inducing a local temporary modulation of the else how continuous membrane governed by normal bending elastic properties. In the high concentration range, a different mechanism results in stable holes induced into the lipid membranes with diameters up to giant extensions.
Emneord: antibiotics; transient pores; micromechanics; membrane structure
|Period||8. Mar 2007|
|Event title||Fluctuating Membrane Pores Induced By Antibacterial Peptides- A Dynamic Model For An Antibiotic Effect: null|
- antibiotics; transient pores; micromechanics; membrane structure