scholarly journals Verapamil prevents the effects of daunomycin on the thermotropic phase transition of model lipid bilayers

1991 ◽  
Vol 279 (2) ◽  
pp. 413-418 ◽  
Author(s):  
J M Canaves ◽  
J A Ferragut ◽  
J M Gonzalez-Ros

High-sensitivity differential scanning calorimetry and fluorescence-depolarization techniques were used to study how the presence of daunomycin and/or verapamil affect the thermotropic behaviour of dipalmitoyl phosphatidylcholine (DPPC) vesicles. Daunomycin, a potent anti-cancer agent, perturbs the thermodynamic parameters associated with the lipid phase transition: it decreases the enthalpy change, lowers the transition temperature and reduces the co-operative behavior of the phospholipid molecules. Verapamil, on the other hand, produces smaller alterations in the lipid phase transition. However, when daunomycin and verapamil are present simultaneously in the DPPC vesicles, it is observed that verapamil prevents, in a concentration-dependent manner, the alteration in the phospholipid phase transition expected from the presence of daunomycin in the bilayer. Furthermore, drug-binding studies suggest that the observed interference of verapamil in the daunomycin/phospholipid interaction occurs without a decrease in the amount of daunomycin bound to the lipid bilayer and without the formation of a daunomycin-verapamil complex. Because of the importance of drug-membrane interactions in anthracycline cytotoxicity, we speculate that the lipid bilayer of biological membranes may provide appropriate sites at which the presence of verapamil influences the activity of daunomycin.

2021 ◽  
Vol 22 (23) ◽  
pp. 13146
Author(s):  
Hanna Pruchnik ◽  
Anna Gliszczyńska ◽  
Aleksandra Włoch

The aim of this work was the evaluation of the physico-chemical properties of a new type of liposomes that are composed of DPPC and bioconjugates of anisic acid with phosphatidylcholine. In particular, the impact of modified anisic acid phospholipids on the thermotropic parameters of liposomes was determined, which is crucial for using them as potential carriers of active substances in cancer therapies. Their properties were determined using three biophysical methods, namely differential scanning calorimetry (DSC), steady-state fluorimetry and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Moreover, temperature studies of liposomes composed of DPPC and bioconjugates of anisic acid with phosphatidylcholine provided information about the phase transition, fluidity regarding chain order, hydration and dynamics. The DSC results show that the main phase transition peak for conjugates of anisic acid with phosphatidylcholine molecules was broadened and shifted to a lower temperature in a concentration- and structure-dependent manner. The ATR-FTIR results and the results of measurements conducted using fluorescent probes located at different regions in the lipid bilayer are in line with DSC. The results show that the new bioconjugates with phosphatidylcholine have a significant impact on the physico-chemical properties of a membrane and cause a decrease in the temperature of the main phase transition. The consequence of this is greater fluidity of the lipid bilayer.


Soft Matter ◽  
2020 ◽  
Vol 16 (33) ◽  
pp. 7696-7703
Author(s):  
Lionel Porcar ◽  
Yuri Gerelli

We measured by neutron reflectometry the loss of asymmetry in solid supported lipid bilayers, revealing an intrinsic interplay between passive lipid flip-flop and lipid phase transition.


1990 ◽  
Vol 68 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Rajan George ◽  
Ruthven N.A.H. Lewis ◽  
Ronald N. McElhaney

The purified Na+, Mg2+-ATPase from the Acholeplasma laidlawii B plasma membrane was reconstituted with dimyristoyl phosphatidylcholine and the lipid thermotropic phase behavior of the proteoliposomes formed was investigated by differential scanning calorimetry. The effect of this ATPase on the host lipid phase transition is markedly dependent on the amount of protein incorporated. At low protein/lipid ratios, the presence of increasing quantities of ATPase in the proteoliposomes increases the temperature and enthalpy while decreasing the cooperativity of the dimyristoyl phosphatidylcholine gel to liquid–crystalline phase transition. At higher protein/lipid ratios, the incorporation of increasing amounts of this enzyme does not further alter the temperature and cooperativity of the phospholipid chain-melting transition, but progressively and markedly decreases the transition enthalpy. Plots of lipid phase transition enthalpy versus protein concentration suggest that at the higher protein/lipid ratios each ATPase molecule removes approximately 1000 dimyristoyl phosphatidylcholine molecules from participation in the cooperative gel to liquid–crystalline phase transition of the bulk lipid phase. These results indicate that this integral transmembrane protein interacts in a complex, concentration-dependent manner with its host phospholipid and that such interactions involve both hydrophobic interactions with the lipid bilayer core and electrostatic interactions with the lipid polar head groups at the bilayer surface.Key words: Acholeplasma laidlawii B, Na+,Mg2+-ATPase, differential scanning calorimetry, lipid-protein interactions.


1979 ◽  
Vol 34 (5-6) ◽  
pp. 406-413 ◽  
Author(s):  
J. Luisetti ◽  
H. Möhwald ◽  
H. J. Galla

Abstract Absorption and fluorescence experiments on pheophytin and chlorophyll containing lipid bilayer vesicles are reported. Pheophytin aggregates on the vesicles are established from an additional red shifted band (at 695 nm) in the absorption spectrum. These aggregates contain pheophytin in an arrangement with the molecular planes of the porphyrin rings being parallel and cover about 10% of the vesicle surface. The lipid phase dissolves pheophytin up to a molar ratio of 15% above the lipid phase transition. This solubility limit decreases hardly on solidification of the lipid.For chlorophyll a containing vesicles the aggregates are not observed in the absorption spectrum. The chlorophyll solubility is about equal to that of pheophytin. This suggests that the phase separa­ tion indicated from fluorescence measurements at temperatures below the lipid phase transition does not lead to the formation of strongly bound chlorophyll aggregates.


1984 ◽  
Vol 62 (11) ◽  
pp. 1134-1150 ◽  
Author(s):  
P. M. Macdonald ◽  
B. D. Sykes ◽  
R. N. McElhaney

The orientational order parameters of monofluoropalmitic acids biosynthetically incorporated into membranes of Acholeplasma laidlawii B in the presence of a large excess of a variety of structurally diverse fatty acids have been determined via 19F nuclear magnetic resonance (19F NMR) spectroscopy. It is demonstrated that these monofluoropalmitic acids are relatively nonperturbing membrane probes based upon physical (differential scanning calorimetry), biochemical (membrane lipid analysis), and biological (growth studies) criteria. 19F NMR is shown to convey the same qualitative and quantitative picture of membrane lipid order provided by 2H-NMR techniques and to be sensitive to the structural characteristics of the membrane fatty acyl chains, as well as to the lipid phase transition. Representatives of each naturally occurring class of fatty acyl chain structures, including straight-chain saturated, methyl-branched, monounsaturated, and alicyclic-ring-substituted fatty acids, were studied and the 19F-NMR order parameters were correlated with the lipid phase transitions (determined calorimetrically). The lipid phase transition was the prime determinant of overall orientational order regardless of fatty acid structure. Effects upon orientational order attributable to specific structural substituents were discernible, but were secondary to the effects of the lipid phase transition. In the gel state, relative overall order was directly proportional to the temperature of the particular lipid phase transition. Not only the overall order, but also the order profile across the membrane was sensitive to the presence of particular structural substituents. In particular, in the gel state specific fatty acyl structures demonstrated a characteristic disordering effect in the membrane order profile. These various observations can be merged to provide a unified picture of the manner in which fatty acyl chain chemistry modulates the physical state of membrane lipids.


2017 ◽  
Vol 14 (130) ◽  
pp. 20170127 ◽  
Author(s):  
Sina Youssefian ◽  
Nima Rahbar ◽  
Christopher R. Lambert ◽  
Steven Van Dessel

Given their amphiphilic nature and chemical structure, phospholipids exhibit a strong thermotropic and lyotropic phase behaviour in an aqueous environment. Around the phase transition temperature, phospholipids transform from a gel-like state to a fluid crystalline structure. In this transition, many key characteristics of the lipid bilayers such as structure and thermal properties alter. In this study, we employed atomistic simulation techniques to study the structure and underlying mechanisms of heat transfer in dipalmitoylphosphatidylcholine (DPPC) lipid bilayers around the fluid–gel phase transformation. To investigate this phenomenon, we performed non-equilibrium molecular dynamics simulations for a range of different temperature gradients. The results show that the thermal properties of the DPPC bilayer are highly dependent on the temperature gradient. Higher temperature gradients cause an increase in the thermal conductivity of the DPPC lipid bilayer. We also found that the thermal conductivity of DPPC is lowest at the transition temperature whereby one lipid leaflet is in the gel phase and the other is in the liquid crystalline phase. This is essentially related to a growth in thermal resistance between the two leaflets of lipid at the transition temperature. These results provide significant new insights into developing new thermal insulation for engineering applications.


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