Asymmetric effects of amphipathic molecules on mechanosensitive channels.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 06 2022
15 06 2022
Historique:
received:
24
02
2022
accepted:
06
06
2022
entrez:
15
6
2022
pubmed:
16
6
2022
medline:
18
6
2022
Statut:
epublish
Résumé
Mechanosensitive (MS) ion channels are primary transducers of mechanical force into electrical and/or chemical intracellular signals. Many diverse MS channel families have been shown to respond to membrane forces. As a result of this intimate relationship with the membrane and proximal lipids, amphipathic compounds exert significant effects on the gating of MS channels. Here, we performed all-atom molecular dynamics (MD) simulations and employed patch-clamp recording to investigate the effect of two amphipaths, Fluorouracil (5-FU) a chemotherapy agent, and the anaesthetic trifluoroethanol (TFE) on structurally distinct mechanosensitive channels. We show that these amphipaths have a profound effect on the bilayer order parameter as well as transbilayer pressure profile. We used bacterial mechanosensitive channels (MscL/MscS) and a eukaryotic mechanosensitive channel (TREK-1) as force-from-lipids reporters and showed that these amphipaths have differential effects on these channels depending on the amphipaths' size and shape as well as which leaflet of the bilayer they incorporate into. 5-FU is more asymmetric in shape and size than TFE and does not penetrate as deep within the bilayer as TFE. Thereby, 5-FU has a more profound effect on the bilayer and channel activity than TFE at much lower concentrations. We postulate that asymmetric effects of amphipathic molecules on mechanosensitive membrane proteins through the bilayer represents a general regulatory mechanism for these proteins.
Identifiants
pubmed: 35705645
doi: 10.1038/s41598-022-14446-w
pii: 10.1038/s41598-022-14446-w
pmc: PMC9200802
doi:
Substances chimiques
Escherichia coli Proteins
0
Fluorouracil
U3P01618RT
Ion Channels
0
Lipid Bilayers
0
Lipids
0
MscL protein, E coli
0
Trifluoroethanol
75-89-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9976Informations de copyright
© 2022. The Author(s).
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