Ions Modulate Key Interactions between pHLIP and Lipid Membranes.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
03 09 2019
03 09 2019
Historique:
received:
20
03
2019
revised:
05
07
2019
accepted:
22
07
2019
pubmed:
20
8
2019
medline:
17
9
2020
entrez:
20
8
2019
Statut:
ppublish
Résumé
The pH-low insertion peptide (pHLIP) is used for targeted delivery of drug cargoes to acidic tissues such as tumors. The extracellular acidosis found in solid tumors triggers pHLIP to transition from a membrane-adsorbed state to fold into a transmembrane α-helix. Different factors influence the acidity required for pHLIP to insert into lipid membranes. One of them is the lipid headgroup composition, which defines the electrostatic profile of the membrane. However, the molecular interactions that drive the adsorption of pHLIP to the bilayer surface are poorly understood. In this study, we combine biophysical experiments and all-atom molecular dynamics simulations to understand the role played by electrostatics in the interaction between pHLIP and a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer. We observed that the solution ionic strength affects the structure of pHLIP at the membrane surface as well as the acidity needed for different steps in the membrane insertion process. In particular, our simulations revealed that an increase in ionic strength affected both pHLIP and the bilayer; the coordination of sodium ions with the C-terminus of pHLIP led to localized changes in helicity, whereas the coordination of sodium ions with the phosphate moiety of the phosphocholine headgroups had a condensing effect on our model bilayer. These results are relevant to our understanding of environmental influences on the ability of pHLIP to adsorb to the cell membrane and are useful in our fundamental understanding of the absorption of pH-responsive peptides and cell-penetrating peptides.
Identifiants
pubmed: 31422821
pii: S0006-3495(19)30623-X
doi: 10.1016/j.bpj.2019.07.034
pmc: PMC6731387
pii:
doi:
Substances chimiques
Ions
0
Membrane Lipids
0
Membrane Proteins
0
Phosphatidylcholines
0
pHLIP protein
0
Sodium Chloride
451W47IQ8X
1-palmitoyl-2-oleoylphosphatidylcholine
TE895536Y5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
920-929Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM120642
Pays : United States
Organisme : NIGMS NIH HHS
ID : R15 GM120676
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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