Cargando…

The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers

We recently published two novel findings where we found the chemotherapy drugs (CDs) thiocolchicoside (TCC) and taxol to induce toroidal type ion pores and the antimicrobial peptide gramicidin S (GS) to induce transient defects in model membranes. Both CD pores and GS defects were induced under the...

Descripción completa

Detalles Bibliográficos
Autor principal: Ashrafuzzaman, Md.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067072/
https://www.ncbi.nlm.nih.gov/pubmed/33808204
http://dx.doi.org/10.3390/membranes11040247
_version_ 1783682715935047680
author Ashrafuzzaman, Md.
author_facet Ashrafuzzaman, Md.
author_sort Ashrafuzzaman, Md.
collection PubMed
description We recently published two novel findings where we found the chemotherapy drugs (CDs) thiocolchicoside (TCC) and taxol to induce toroidal type ion pores and the antimicrobial peptide gramicidin S (GS) to induce transient defects in model membranes. Both CD pores and GS defects were induced under the influence of an applied transmembrane potential (≈100 mV), which was inspected using the electrophysiology record of membrane currents (ERMCs). In this article, I address the regulation of the membrane adsorption and pore formation of CDs due to GS-induced possible alterations of lipid bilayer physical properties. In ERMCs, low micromolar (≥1 μM) GS concentrations in the aqueous phase were found to cause an induction of defects in lipid bilayers, but nanomolar (nM) concentration GS did nothing. For the binary presence of CDs and GS in the membrane-bathing aqueous phase, the TCC pore formation potency is found to increase considerably due to nM concentration GS in buffer. This novel result resembles our recently reported finding that due to the binary aqueous presence of two AMPs (gramicidin A or alamethicin and GS), the pore or defect-forming potency of either AMP increases considerably. To reveal the underlying molecular mechanisms, the influence of GS (0–400 nM) on the quantitative liposome (membrane) adsorption of CD molecules, colchicine and TCC, was tested. I used the recently patented direct detection method, which helps detect the membrane active agents directly at the membrane in the mole fraction relative to its concentrations in aqueous phase. We find that GS, at concentrations known to do nothing to the lipid bilayer electrical barrier properties in ERMCs, increases the membrane adsorption (membrane uptake) of CDs considerably. This phenomenological finding along with the GS effects on CD-induced membrane conductance increase helps predict an important conclusion. The binary presence of AMPs alongside CDs in the lipid membrane vicinity may work toward enhancing the physical adsorption and pore formation potency of CDs in lipid bilayers. This may help understand why CDs cause considerable cytotoxicity.
format Online
Article
Text
id pubmed-8067072
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80670722021-04-25 The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers Ashrafuzzaman, Md. Membranes (Basel) Article We recently published two novel findings where we found the chemotherapy drugs (CDs) thiocolchicoside (TCC) and taxol to induce toroidal type ion pores and the antimicrobial peptide gramicidin S (GS) to induce transient defects in model membranes. Both CD pores and GS defects were induced under the influence of an applied transmembrane potential (≈100 mV), which was inspected using the electrophysiology record of membrane currents (ERMCs). In this article, I address the regulation of the membrane adsorption and pore formation of CDs due to GS-induced possible alterations of lipid bilayer physical properties. In ERMCs, low micromolar (≥1 μM) GS concentrations in the aqueous phase were found to cause an induction of defects in lipid bilayers, but nanomolar (nM) concentration GS did nothing. For the binary presence of CDs and GS in the membrane-bathing aqueous phase, the TCC pore formation potency is found to increase considerably due to nM concentration GS in buffer. This novel result resembles our recently reported finding that due to the binary aqueous presence of two AMPs (gramicidin A or alamethicin and GS), the pore or defect-forming potency of either AMP increases considerably. To reveal the underlying molecular mechanisms, the influence of GS (0–400 nM) on the quantitative liposome (membrane) adsorption of CD molecules, colchicine and TCC, was tested. I used the recently patented direct detection method, which helps detect the membrane active agents directly at the membrane in the mole fraction relative to its concentrations in aqueous phase. We find that GS, at concentrations known to do nothing to the lipid bilayer electrical barrier properties in ERMCs, increases the membrane adsorption (membrane uptake) of CDs considerably. This phenomenological finding along with the GS effects on CD-induced membrane conductance increase helps predict an important conclusion. The binary presence of AMPs alongside CDs in the lipid membrane vicinity may work toward enhancing the physical adsorption and pore formation potency of CDs in lipid bilayers. This may help understand why CDs cause considerable cytotoxicity. MDPI 2021-03-30 /pmc/articles/PMC8067072/ /pubmed/33808204 http://dx.doi.org/10.3390/membranes11040247 Text en © 2021 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Ashrafuzzaman, Md.
The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers
title The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers
title_full The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers
title_fullStr The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers
title_full_unstemmed The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers
title_short The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers
title_sort antimicrobial peptide gramicidin s enhances membrane adsorption and ion pore formation potency of chemotherapy drugs in lipid bilayers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067072/
https://www.ncbi.nlm.nih.gov/pubmed/33808204
http://dx.doi.org/10.3390/membranes11040247
work_keys_str_mv AT ashrafuzzamanmd theantimicrobialpeptidegramicidinsenhancesmembraneadsorptionandionporeformationpotencyofchemotherapydrugsinlipidbilayers
AT ashrafuzzamanmd antimicrobialpeptidegramicidinsenhancesmembraneadsorptionandionporeformationpotencyofchemotherapydrugsinlipidbilayers