Interaction of LL-37 with model membrane systems of different complexity: influence of the lipid matrix.
Sevcsik. E E; Pabst. G G; Richter. W W; Danner. S S; Amenitsch. H H; Lohner. K K
Key Findings
- Effects seen on single‑layer membranes don’t match those on double‑layer (bilayer) membranes
- Each of the four main lipids (PC, PE, PG, PS) shows a distinct response to LL‑37
- LL‑37 prefers lipids with looser packing; tighter‑packed lipids resist it
- In mixed‑lipid membranes, one lipid (not necessarily the charged one) dominates how LL‑37 interacts
- Overall, membrane charge is just one of several factors—packing density, hydrogen‑bonding ability, and lipid shape also shape LL‑37’s activity
Practical Outcomes
- When using LL‑37 supplements or topical formulations, expect its activity to vary with the type of cell membranes you’re targeting. Formulations that mimic looser, less‑packed lipid environments may boost its effectiveness, while tightly packed membranes could blunt its action. This insight helps you choose delivery methods (e.g., lipid carriers) that favor the right membrane characteristics, but the study doesn’t give specific dosing advice.
Summary
LL-37, a human antimicrobial peptide, sticks to cell membranes in ways that depend more on how tightly the membrane lipids are packed and their shape than just on the membrane’s electric charge. This means its effects can change a lot depending on the exact mix of fats in the membrane.
Abstract
As the main difference between bacterial and mammalian cell membranes is their net charge, the focal point of consideration in many model membrane experiments with antimicrobial peptides is lipid headgroup charge. We studied the interaction of the human multifunctional peptide LL-37 with single phospholipid monolayers, bilayers, and bilayers composed of binary mixtures of the four phospholipid species predominantly used in model membrane experiments (phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylserine). We found that 1), the effects on single lipid monolayers are not comparable to those on the corresponding bilayers; 2), there are four different effects of LL-37 on bilayers of the four lipids; 3), the preference of LL-37 for the specific lipids is roughly inversely related to chain packing density; and 4), in the binary lipid mixtures, one lipid-and not necessarily the charged one--generally governs the mode of lipid/peptide interaction. Thus, our results show that lipid net charge is not the decisive factor determining the membrane-perturbing mechanism of LL-37, but only one of several parameters, among them packing density, the ability to form intermolecular H-bonds, and lipid molecular shape, which emphasizes how profoundly the choice of the model system can influence the outcome of a study of lipid/peptide interaction.
Study Information
pubmed
2008
2008-03-07T00:00:00.000Z
10.1529/biophysj.107.123620
110
51