Interactions of intrinsically disordered peptides with phospholipid bilayers
(2024)- Abstract
- The main goal of this thesis has been to investigate the interaction of the intrinsically disordered peptide Histatin 5 (Hst5), with phospholipid bilayers, using a mixture of experimental and computational techniques, such as, small- angle X-ray scattering, circular dichroism, neutron reflectometry, quartz-crystal microbalance with dissipation monitoring, atomistic molecular dynamics simulations, and coarse-grained Monte Carlo simulations. Hst5 is of particular interest due to its known antimicrobial effects, where it acts as the first defense against fungal infections in the mouth. With antimicrobial resistance being an increasingly and serious threat against world health, alternative treatments to common antimicrobial agents are needed,... (More)
- The main goal of this thesis has been to investigate the interaction of the intrinsically disordered peptide Histatin 5 (Hst5), with phospholipid bilayers, using a mixture of experimental and computational techniques, such as, small- angle X-ray scattering, circular dichroism, neutron reflectometry, quartz-crystal microbalance with dissipation monitoring, atomistic molecular dynamics simulations, and coarse-grained Monte Carlo simulations. Hst5 is of particular interest due to its known antimicrobial effects, where it acts as the first defense against fungal infections in the mouth. With antimicrobial resistance being an increasingly and serious threat against world health, alternative treatments to common antimicrobial agents are needed, where antimicrobial peptides being one option. It is therefore important to understand the mechanism behind their effect, to be able to utilize their properties correctly in pharmaceuticals. In the first study of this thesis, Hst5 was found to spontaneously translocate a phospholipid bilayer, without affecting the structural integrity of the bilayer, thus resulting in a peptide cushion between the supported bilayer and the solid surface. This formation is in line with the antimicrobial effect of Hst5, and has therefore been used as an indication of antimicrobial effect throughout the work conducted in this thesis. The experimental conditions needed for the cushion formation was further determined. In the second study, the role of the amino acid histidine, which is frequently found in Hst5, was investigated to determine its role in the translocation process. The results showed that the penetration depth into the bilayer increases with increasing number of histidines. In this study, it was also suggested that not only the number of histidines, but also their position were important, therefore, a study regarding the order of amino acids was conducted as the ongoing study presented in this thesis. The results indicate a difference in interaction, dependent on the sequence order, however, the underlying explanation is not yet understood. Furthermore, the sequence length of Hst5 was investigated in the third study of this thesis, which only showed small differences at 10 mM NaCl concentration, while in 150 mM NaCl, both the shorter and longer variant display interactions with the bilayer, while Hst5 does not. The final study included in this thesis concerns a different peptide called KEIF, which is the intrinsically disordered N-terminal of magnesium transporter A found in Escherichia coli. This study was conducted with the aim to investigate the hypothesis that surface active intrinsically disordered peptides gain structure upon adsorption, which is related to their function. The peptide became more structured upon adsorption, supporting the presented hypothesis. (Less)
- Abstract (Swedish)
- The main goal of this thesis has been to investigate the interaction of the intrinsically disordered peptide Histatin 5 (Hst5), with phospholipid bilayers, using a mixture of experimental and computational techniques, such as, small- angle X-ray scattering, circular dichroism, neutron reflectometry, quartz-crystal microbalance with dissipation monitoring, atomistic molecular dynamics simulations, and coarse-grained Monte Carlo simulations. Hst5 is of particular interest due to its known antimicrobial effects, where it acts as the first defense against fungal infections in the mouth. With antimicrobial resistance being an increasingly and serious threat against world health, alternative treatments to common antimicrobial agents are needed,... (More)
- The main goal of this thesis has been to investigate the interaction of the intrinsically disordered peptide Histatin 5 (Hst5), with phospholipid bilayers, using a mixture of experimental and computational techniques, such as, small- angle X-ray scattering, circular dichroism, neutron reflectometry, quartz-crystal microbalance with dissipation monitoring, atomistic molecular dynamics simulations, and coarse-grained Monte Carlo simulations. Hst5 is of particular interest due to its known antimicrobial effects, where it acts as the first defense against fungal infections in the mouth. With antimicrobial resistance being an increasingly and serious threat against world health, alternative treatments to common antimicrobial agents are needed, where antimicrobial peptides being one option. It is therefore important to understand the mechanism behind their effect, to be able to utilize their properties correctly in pharmaceuticals. In the first study of this thesis, Hst5 was found to spontaneously translocate a phospholipid bilayer, without affecting the structural integrity of the bilayer, thus resulting in a peptide cushion between the supported bilayer and the solid surface. This formation is in line with the antimicrobial effect of Hst5, and has therefore been used as an indication of antimicrobial effect throughout the work conducted in this thesis. The experimental conditions needed for the cushion formation was further determined. In the second study, the role of the amino acid histidine, which is frequently found in Hst5, was investigated to determine its role in the translocation process. The results showed that the penetration depth into the bilayer increases with increasing number of histidines. In this study, it was also suggested that not only the number of histidines, but also their position were important, therefore, a study regarding the order of amino acids was conducted as the ongoing study presented in this thesis. The results indicate a difference in interaction, dependent on the sequence order, however, the underlying explanation is not yet understood. Furthermore, the sequence length of Hst5 was investigated in the third study of this thesis, which only showed small differences at 10 mM NaCl concentration, while in 150 mM NaCl, both the shorter and longer variant display interactions with the bilayer, while Hst5 does not. The final study included in this thesis concerns a different peptide called KEIF, which is the intrinsically disordered N-terminal of magnesium transporter A found in Escherichia coli. This study was conducted with the aim to investigate the hypothesis that surface active intrinsically disordered peptides gain structure upon adsorption, which is related to their function. The peptide became more structured upon adsorption, supporting the presented hypothesis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/f870c3c7-f454-4b87-9259-82562558b9c4
- author
- Eriksson Skog, Amanda LU
- supervisor
- opponent
-
- Doctor Cramer Pedersen, Martin, Niels Bohr Institute and the Niels Bohr International Academy at the University of Copenhagen.
- organization
- publishing date
- 2024
- type
- Thesis
- publication status
- published
- subject
- keywords
- intrinsically disordered peptides, CD, SAXS, Antimicrbial peptide, peptide-lipid interaction, NR, QCM-D, MC, MD
- pages
- 241 pages
- publisher
- Lund University
- defense location
- Kemicentrum KC:A.
- defense date
- 2024-12-06 09:00:00
- ISBN
- 978-91-8096-070-0
- 978-91-8096-071-7
- language
- English
- LU publication?
- yes
- id
- f870c3c7-f454-4b87-9259-82562558b9c4
- date added to LUP
- 2024-10-21 14:21:32
- date last changed
- 2025-04-04 15:14:07
@phdthesis{f870c3c7-f454-4b87-9259-82562558b9c4,
abstract = {{The main goal of this thesis has been to investigate the interaction of the intrinsically disordered peptide Histatin 5 (Hst5), with phospholipid bilayers, using a mixture of experimental and computational techniques, such as, small- angle X-ray scattering, circular dichroism, neutron reflectometry, quartz-crystal microbalance with dissipation monitoring, atomistic molecular dynamics simulations, and coarse-grained Monte Carlo simulations. Hst5 is of particular interest due to its known antimicrobial effects, where it acts as the first defense against fungal infections in the mouth. With antimicrobial resistance being an increasingly and serious threat against world health, alternative treatments to common antimicrobial agents are needed, where antimicrobial peptides being one option. It is therefore important to understand the mechanism behind their effect, to be able to utilize their properties correctly in pharmaceuticals. In the first study of this thesis, Hst5 was found to spontaneously translocate a phospholipid bilayer, without affecting the structural integrity of the bilayer, thus resulting in a peptide cushion between the supported bilayer and the solid surface. This formation is in line with the antimicrobial effect of Hst5, and has therefore been used as an indication of antimicrobial effect throughout the work conducted in this thesis. The experimental conditions needed for the cushion formation was further determined. In the second study, the role of the amino acid histidine, which is frequently found in Hst5, was investigated to determine its role in the translocation process. The results showed that the penetration depth into the bilayer increases with increasing number of histidines. In this study, it was also suggested that not only the number of histidines, but also their position were important, therefore, a study regarding the order of amino acids was conducted as the ongoing study presented in this thesis. The results indicate a difference in interaction, dependent on the sequence order, however, the underlying explanation is not yet understood. Furthermore, the sequence length of Hst5 was investigated in the third study of this thesis, which only showed small differences at 10 mM NaCl concentration, while in 150 mM NaCl, both the shorter and longer variant display interactions with the bilayer, while Hst5 does not. The final study included in this thesis concerns a different peptide called KEIF, which is the intrinsically disordered N-terminal of magnesium transporter A found in Escherichia coli. This study was conducted with the aim to investigate the hypothesis that surface active intrinsically disordered peptides gain structure upon adsorption, which is related to their function. The peptide became more structured upon adsorption, supporting the presented hypothesis.}},
author = {{Eriksson Skog, Amanda}},
isbn = {{978-91-8096-070-0}},
keywords = {{intrinsically disordered peptides; CD; SAXS; Antimicrbial peptide; peptide-lipid interaction; NR; QCM-D; MC; MD}},
language = {{eng}},
publisher = {{Lund University}},
school = {{Lund University}},
title = {{Interactions of intrinsically disordered peptides with phospholipid bilayers}},
url = {{https://lup.lub.lu.se/search/files/197976176/Avhandling_Amanda_Eriksson_Skog_LUCRIS.pdf}},
year = {{2024}},
}