Membrane Core-Specific Antimicrobial Action of Cathelicidin LL-37 Peptide Switches Between Pore and Nanofibre Formation.
Shahmiri. Mahdi M; Enciso. Marta M; Adda. Christopher G CG; Smith. Brian J BJ; Perugini. Matthew A MA; Mechler. Adam A
Key Findings
- LL‑37 forms pores in bilayers made of unsaturated phospholipids.
- With saturated phospholipids, LL‑37 causes the membrane to reorganize into helical‑rich fibrous peptide‑lipid superstructures.
- The mode of action is dictated by the alkyl‑chain saturation of the membrane lipids, not by the head‑group chemistry.
- These insights point to new ways to design antimicrobial peptides.
Practical Outcomes
- For biohackers, this study doesn’t provide a direct protocol or dosage recommendation for LL‑37 use. It suggests that the peptide’s effects could vary widely depending on the lipid composition of cells, making self‑experimentation risky and unpredictable. At present, the findings are more relevant for drug developers than for personal health optimization.
Summary
Scientists discovered that the human antimicrobial peptide LL‑37 changes how it attacks cell membranes depending on the type of fat chains in the membrane: it makes holes in membranes with unsaturated fats and builds fiber‑like structures with saturated fats. This shows the peptide’s action is driven by the core of the membrane, not just the surface head groups.
Abstract
Membrane-disrupting antimicrobial peptides provide broad-spectrum defence against localized bacterial invasion in a range of hosts including humans. The most generally held consensus is that targeting to pathogens is based on interactions with the head groups of membrane lipids. Here we show that the action of LL-37, a human antimicrobial peptide switches the mode of action based on the structure of the alkyl chains, and not the head groups of the membrane forming lipids. We demonstrate that LL-37 exhibits two distinct interaction pathways: pore formation in bilayers of unsaturated phospholipids and membrane modulation with saturated phospholipids. Uniquely, the membrane modulation yields helical-rich fibrous peptide-lipid superstructures. Our results point at alternative design strategies for peptide antimicrobials.
Study Information
pubmed
2016
2016-11-30T00:00:00.000Z
10.1038/srep38184
63
57