Translocation of Antimicrobial Peptides across Model Membranes : The Role of Peptide Chain Length
(2024) In Molecular Pharmaceutics 21(8). p.4082-4097- Abstract
Cushioned lipid bilayers are structures consisting of a lipid bilayer supported on a solid substrate with an intervening layer of soft material. They offer possibilities for studying the behavior and interactions of biological membranes more accurately under physiological conditions. In this work, we continue our studies of cushion formation induced by histatin 5 (24Hst5), focusing on the effect of the length of the peptide chain. 24Hst5 is a short, positively charged, intrinsically disordered saliva peptide, and here, both a shorter (14Hst5) and a longer (48Hst5) peptide variant were evaluated. Experimental surface active techniques were combined with coarse-grained Monte Carlo simulations to... (More)
Cushioned lipid bilayers are structures consisting of a lipid bilayer supported on a solid substrate with an intervening layer of soft material. They offer possibilities for studying the behavior and interactions of biological membranes more accurately under physiological conditions. In this work, we continue our studies of cushion formation induced by histatin 5 (24Hst5), focusing on the effect of the length of the peptide chain. 24Hst5 is a short, positively charged, intrinsically disordered saliva peptide, and here, both a shorter (14Hst5) and a longer (48Hst5) peptide variant were evaluated. Experimental surface active techniques were combined with coarse-grained Monte Carlo simulations to obtain information about these peptides. Results show that at 10 mM NaCl, both the shorter and the longer peptide variants behave like 24Hst5 and a cushion below the bilayer is formed. At 150 mM NaCl, however, no interaction is observed for 24Hst5. On the contrary, a cushion is formed both in the case of 14Hst5 and 48Hst5, and in the latter, an additional thick, diffuse, and highly hydrated layer of peptide and lipid molecules is formed, on top of the bilayer. Similar trends were observed from the simulations, which allowed us to hypothesize that positively charged patches of the amino acids lysine and arginine in all three peptides are essential for them to interact with and translocate over the bilayer. We therefore hypothesize that electrostatic interactions are important for the interaction between the solid-supported lipid bilayers and the peptide depending on the linear charge density through the primary sequence and the positively charged patches in the sequence. The understanding of how, why, and when the cushion is formed opens up the possibility for this system to be used in the research and development of new drugs and pharmaceuticals.
(Less)
- author
- Skog, Amanda E. LU ; Paracini, Nicolò ; Gerelli, Yuri and Skepö, Marie LU
- organization
- publishing date
- 2024-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- antifungal, antimicrobial, cushion formation, histatin 5, lipid bilayers, model membrane, peptide, saliva, solid-supported lipid bilayers
- in
- Molecular Pharmaceutics
- volume
- 21
- issue
- 8
- pages
- 16 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:85198519206
- pmid:38993084
- ISSN
- 1543-8384
- DOI
- 10.1021/acs.molpharmaceut.4c00450
- language
- English
- LU publication?
- yes
- id
- f1b5154b-812b-43c5-9eac-b2460aa8fbe1
- date added to LUP
- 2024-09-10 16:51:38
- date last changed
- 2024-10-08 21:46:17
@article{f1b5154b-812b-43c5-9eac-b2460aa8fbe1,
abstract = {{<p>Cushioned lipid bilayers are structures consisting of a lipid bilayer supported on a solid substrate with an intervening layer of soft material. They offer possibilities for studying the behavior and interactions of biological membranes more accurately under physiological conditions. In this work, we continue our studies of cushion formation induced by histatin 5 (<sup>24</sup>Hst5), focusing on the effect of the length of the peptide chain. <sup>24</sup>Hst5 is a short, positively charged, intrinsically disordered saliva peptide, and here, both a shorter (<sup>14</sup>Hst5) and a longer (<sup>48</sup>Hst5) peptide variant were evaluated. Experimental surface active techniques were combined with coarse-grained Monte Carlo simulations to obtain information about these peptides. Results show that at 10 mM NaCl, both the shorter and the longer peptide variants behave like <sup>24</sup>Hst5 and a cushion below the bilayer is formed. At 150 mM NaCl, however, no interaction is observed for <sup>24</sup>Hst5. On the contrary, a cushion is formed both in the case of <sup>14</sup>Hst5 and <sup>48</sup>Hst5, and in the latter, an additional thick, diffuse, and highly hydrated layer of peptide and lipid molecules is formed, on top of the bilayer. Similar trends were observed from the simulations, which allowed us to hypothesize that positively charged patches of the amino acids lysine and arginine in all three peptides are essential for them to interact with and translocate over the bilayer. We therefore hypothesize that electrostatic interactions are important for the interaction between the solid-supported lipid bilayers and the peptide depending on the linear charge density through the primary sequence and the positively charged patches in the sequence. The understanding of how, why, and when the cushion is formed opens up the possibility for this system to be used in the research and development of new drugs and pharmaceuticals.</p>}},
author = {{Skog, Amanda E. and Paracini, Nicolò and Gerelli, Yuri and Skepö, Marie}},
issn = {{1543-8384}},
keywords = {{antifungal; antimicrobial; cushion formation; histatin 5; lipid bilayers; model membrane; peptide; saliva; solid-supported lipid bilayers}},
language = {{eng}},
number = {{8}},
pages = {{4082--4097}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Molecular Pharmaceutics}},
title = {{Translocation of Antimicrobial Peptides across Model Membranes : The Role of Peptide Chain Length}},
url = {{http://dx.doi.org/10.1021/acs.molpharmaceut.4c00450}},
doi = {{10.1021/acs.molpharmaceut.4c00450}},
volume = {{21}},
year = {{2024}},
}