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

Membranes ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 247
Author(s):  
Md. Ashrafuzzaman
Keyword(s):  
Antimicrobial Peptide ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Aqueous Phase ◽  
Pore Formation ◽  
Molecular Mechanisms ◽  
Important Conclusion ◽  
Liposome Membrane ◽  
Chemotherapy Drugs ◽  
Gramicidin S

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.

scholarly journals Elementary processes of antimicrobial peptide PGLa-induced pore formation in lipid bilayers

2018 ◽  
Vol 1860 (11) ◽  
pp. 2262-2271 ◽  
Author(s):  
Farliza Parvez ◽  
Jahangir Md. Alam ◽  
Hideo Dohra ◽  
Masahito Yamazaki
Keyword(s):  
Antimicrobial Peptide ◽  
Lipid Bilayers ◽  
Pore Formation ◽  
Elementary Processes

scholarly journals Effect of membrane potential on pore formation by the antimicrobial peptide magainin 2 in lipid bilayers

2020 ◽  
Vol 1862 (10) ◽  
pp. 183381
Author(s):  
Md. Mamun Or Rashid ◽  
Md. Mizanur Rahman Moghal ◽  
Md. Masum Billah ◽  
Moynul Hasan ◽  
Masahito Yamazaki
Keyword(s):  
Membrane Potential ◽  
Antimicrobial Peptide ◽  
Lipid Bilayers ◽  
Pore Formation

Atomistic Simulation of Pore Formation in Lipid Bilayers in the Presence of Dimethylsulfoxide: Further Evidence for Entropic Driven Pore Formation

2008 ◽  
Author(s):  
Raghava Alapati ◽  
Dorel Moldovan ◽  
Ram Devireddy
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Pore Formation ◽  
Configurational Entropy ◽  
Line Tension ◽  
Nucleation Theory ◽  
Classical Nucleation Theory ◽  
Pore Shape ◽  
Dmso Concentration ◽  
Pore Nucleation

In a recent study, Moldovan et al [1] have demonstrated that in the presence of 11.3 mol% dimethylsulfoxide (DMSO) a pore can nucleate and grow spontaneously in a lipid bilayer even in the absence of an externally applied stresses or electric field. The authors rationalized the spontaneous pore nucleation, in the absence of any external driving force, by considering the combined effect of the entropy of pore shape fluctuation and the significant decrease of the bilayer line tension in the presence of DMSO. Building on the classical nucleation theory developed three decades ago by Lister [2] the authors propose a new formulation for the bilayer free energy that incorporates the pore shape configurational entropy. According to this study, in the presence of DMSO, the pore nucleates spontaneously and grows provided the bilayer line tension decreases below a threshold value, λ. In this study we report our recent simulation results on the effect of DMSO concentration on both bilayer line tension and bilayer structural stability with respect to pore nucleation. The lipid bilayer systems investigated in this study by molecular dynamics (MD) consists of 96 molecules (48 in each leaflet) of dimyristoylphosphatidylcholine (DMPC) immersed in DMSO-water solutions at various concentrations. In all MD simulations reported the bilayer systems were followed over 100 ns. Our simulations results indicate the existence of a critical DMSO concentration below which there are no pores nucleated in the lipid bilayers. Our findings corroborate and complement the entropy-based pore nucleation model proposed earlier by Moldovan et al. [1].

Molecular Mechanism of Action of β-Hairpin Antimicrobial Peptide Arenicin: Oligomeric Structure in Dodecylphosphocholine Micelles and Pore Formation in Planar Lipid Bilayers

Biochemistry ◽  
2011 ◽  
Vol 50 (28) ◽  
pp. 6255-6265 ◽  
Author(s):  
Zakhar O. Shenkarev ◽  
Sergey V. Balandin ◽  
Kirill I. Trunov ◽  
Alexander S. Paramonov ◽  
Stanislav V. Sukhanov ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Molecular Mechanism ◽  
Lipid Bilayers ◽  
Mechanism Of Action ◽  
Pore Formation ◽  
Planar Lipid Bilayers ◽  
Oligomeric Structure ◽  
Molecular Mechanism Of Action

scholarly journals Cell Surface Binding and Lipid Interactions behind Chemotherapy-Drug-Induced Ion Pore Formation in Membranes

Membranes ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 501
Author(s):  
Md. Ashrafuzzaman ◽  
Zahid Khan ◽  
Ashwaq Alqarni ◽  
Mohammad Alanazi ◽  
Mohammad Shahabul Alam
Keyword(s):  
Cell Surface ◽  
Molecular Interactions ◽  
Pore Formation ◽  
Molecular Mechanisms ◽  
Surface Membrane ◽  
Drug Distribution ◽  
Surface Binding ◽  
Cell Surface Membrane ◽  
Chemotherapy Drugs ◽  
Cell Surface Binding

Chemotherapy drugs (CDs) disrupt the lipid membrane’s insulation properties by inducing stable ion pores across bilayer membranes. The underlying molecular mechanisms behind pore formation have been revealed in this study using several methods that confirm molecular interactions and detect associated energetics of drugs on the cell surface in general and in lipid bilayers in particular. Liposome adsorption and cell surface binding of CD colchicine has been demonstrated experimentally. Buffer dissolved CDs were considerably adsorbed in the incubated phospholipid liposomes, measured using the patented ‘direct detection method’. The drug adsorption process is regulated by the membrane environment, demonstrated in cholesterol-containing liposomes. We then detailed the phenomenology and energetics of the low nanoscale dimension cell surface (membrane) drug distribution, using atomic force microscopy (AFM) imaging what addresses the surface morphology and measures adhesion force (reducible to adhesive energy). Liposome adsorption and cell surface binding data helped model the cell surface drug distribution. The underlying molecular interactions behind surface binding energetics of drugs have been addressed in silico numerical computations (NCs) utilizing the screened Coulomb interactions among charges in a drug–drug/lipid cluster. Molecular dynamics (MD) simulations of the CD-lipid complexes detected primarily important CD-lipid electrostatic and van der Waals (vdW) interaction energies. From the energetics point of view, both liposome and cell surface membrane adsorption of drugs are therefore obvious findings. Colchicine treated cell surface AFM images provide a few important phenomenological conclusions, such as drugs bind generally with the cell surface, bind independently as well as in clusters of various sizes in random cell surface locations. The related adhesion energy decreases with increasing drug cluster size before saturating for larger clusters. MD simulation detected electrostatic and vdW and NC-derived charge-based interactions explain molecularly of the cause of cell surface binding of drugs. The membrane binding/association of drugs may help create drug–lipid complexes with specific energetics and statistically lead to the creation of ion channels. We reveal here crucial molecular understanding and features of the pore formation inside lipid membranes that may be applied universally for most of the pore-forming existing agents and novel candidate drugs.

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