Transport of Ca2+ by diltiazem across the lipid bilayer in model liposomes

1992 ◽  
Vol 70 (7) ◽  
pp. 608-612 ◽  
Author(s):  
Vettai S. Ananthanarayanan ◽  
Lorne B. Taylor ◽  
Samuel Pirritano

The calcium channel antagonist diltiazem was examined for its ability to translocate Ca2+ from an aqueous medium to the nonpolar lipid milieu. We monitored the spectral changes caused by the drug-mediated cation transport at 37 °C in unilamellar vesicles made of dimyristoyl phosphatidylcholine (DMPC) and containing the calcium-sensitive dye arsenazo III trapped inside. Vesicle leakage or membrane fusion caused by diltiazem was assessed by the use of vesicles containing fluorescent indicators. These effects were, however, found to be insignificant compared with ion transport. The transport was negligible at temperatures below the liquid crystalline to gel transition temperature of DMPC indicating a carrier mechanism of ion transport. A quantitative analysis of the transport kinetics indicated that a 1:2 Ca +-drug complex is formed inside the lipid. The calcium ionophoretic ability of diltiazem, combined with other related data, suggests a possible role for Ca2+ in the conformation of the drug in the lipid membrane milieu and in its interaction with the calcium channel.Key words: calcium channel antagonists, diltiazem, Ca2+ ionophore, liposomes, drug-Ca2+ complex.

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 192
Author(s):  
Kinga Burdach ◽  
Dagmara Tymecka ◽  
Aneta Urban ◽  
Robert Lasek ◽  
Dariusz Bartosik ◽  
...  

The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic lipopeptides belong to the class of the compounds which may fulfill this requirement. In this paper, we describe two linear analogues of battacin with modified acyl chains to tune the balance between the hydrophilic and hydrophobic portion of lipopeptides. We demonstrate that both compounds display antimicrobial activity with the lowest values of minimum inhibitory concentrations found for Gram-positive pathogens. Therefore, their mechanism of action was evaluated on a molecular level using model lipid films mimicking the membrane of Gram-positive bacteria. The surface pressure measurements revealed that both lipopeptides show ability to bind and incorporate into the lipid monolayers, resulting in decreased ordering of lipids and membrane fluidization. Atomic force microscopy (AFM) imaging demonstrated that the exposure of the model bilayers to lipopeptides leads to a transition from the ordered gel phase to disordered liquid crystalline phase. This observation was confirmed by attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) results, which revealed that lipopeptide action causes a substantial increase in the average tilt angle of lipid acyl chains with respect to the surface normal to compensate for lipopeptide insertion into the membrane. Moreover, the peptide moieties in both molecules do not adopt any well-defined secondary structure upon binding with the lipid membrane. It was also observed that a small difference in the structure of a lipophilic chain, altering the balance between hydrophobic and hydrophilic portion of the molecules, results in different insertion depth of the active compounds.


2006 ◽  
Vol 595 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Osamu Shirai ◽  
Yumi Yoshida ◽  
Sorin Kihara ◽  
Toshihiko Ohnuki ◽  
Akihiro Uehara ◽  
...  

Author(s):  
Kai Hashino ◽  
Daiya Mombayashi ◽  
Yuto Nakatani ◽  
Azusa Oshima ◽  
Masumi Yamaguchi ◽  
...  

Abstract Lipid bilayers suspended over microwells on Si substrates are promising platforms for nanobiodevices that mimic cell membranes. Using the biotin-avidin interaction, we have succeeded in selectively arranging vesicles on the freestanding region of a lipid bilayer. When ternary lipid mixtures of saturated lipid, unsaturated lipid, and cholesterol are used, they separate into liquid-order (Lo) and liquid-crystalline (Lα) domains. A freestanding lipid bilayer prefers the Lα-phase over the Lo-phase because of the difference in their flexibility. In addition, the type of biotinylated lipid determines whether it is localized in the Lα-phase domain or the Lo-phase domain. As a result, the biotinylated unsaturated lipids localized in the Lα-phase domain aggregate in the freestanding lipid bilayer, and vesicles labeled with biotin selectively bind to the freestanding lipid bilayer by the biotin-avidin interaction. This technique helps to introduce biomolecules into the freestanding lipid bilayer of nanobiodevices via vesicles.


Langmuir ◽  
2012 ◽  
Vol 28 (30) ◽  
pp. 10980-10987 ◽  
Author(s):  
Seung Jae Lee ◽  
Hyeun Hwan An ◽  
Won Bae Han ◽  
Hee-Soo Kim ◽  
Chong S. Yoon

2011 ◽  
Vol 40 (5) ◽  
pp. 486-488 ◽  
Author(s):  
Keisuke Sasakura ◽  
Osamu Shirai ◽  
Kei Hichiri ◽  
Maiko Goda-Tsutsumi ◽  
Seiya Tsujimura ◽  
...  

2008 ◽  
Vol 53 (22) ◽  
pp. 6372-6379 ◽  
Author(s):  
Lucia Becucci ◽  
Massimo Innocenti ◽  
Emanuele Salvietti ◽  
Alessio Rindi ◽  
Irene Pasquini ◽  
...  

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