1. Interaction of imatinib with liposomes: voltammetric and AFM characterization
Laura Tugulea, Ana-Maria Oliveira-Brett, Victor C Diculescu, Marilene Vivan, Ana-Maria Chiorcea-Paquim Bioelectrochemistry . 2009 Feb;74(2):278-88. doi: 10.1016/j.bioelechem.2008.10.003.
The interaction of imatinib with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 2-oleoyl-1-stearoyl-sn-glycero-3-phosphocholine (OSPC) liposomes and the adsorption of DPPC and OSPC were studied using atomic force microscopy (AFM) at highly oriented pyrolytic graphite (HOPG) and differential pulse voltammetry at glassy carbon electrode (GCE). The HOPG induces the rupture of the liposomes and allows the lipids to adsorb along one of the three axes of symmetry of the HOPG basal planes, forming well-ordered lamellar structures. After interaction, both DPPC monolayers and DPPC-imatinib complexes are adsorbed onto HOPG. The OSPC-imatinib complexes self-organize only into ordered but larger domains of parallel stripes that maintain the threefold symmetry of the HOPG, due to an easier imatinib penetration into the unsaturated OSPC liposome bilayers. The voltammetric results show that upon interaction, the electrochemical active moiety of imatinib is incorporated into the lipid bilayer becoming unavailable to the GCE surface for oxidation, leading to local structural modifications of the lipid bilayer which were also electrochemically detected. A model is proposed for the liposome-imatinib interaction considering that imatinib interacts primarily by van der Waals and hydrogen bonds with the phosphatidylcholine headgroups, leading to defects in the liposome bilayer and allowing further incorporation of imatinib into the liposome lamellae.
2. Interaction of exogenous hypochlorite or hypochlorite produced by myeloperoxidase + H2O2 + Cl- system with unsaturated phosphatidylcholines
A N Osipov, J Arnhold, J Schiller, O M Panasenko Biochemistry (Mosc) . 2002 Aug;67(8):889-900. doi: 10.1023/a:1019914604011.
The interaction between unsaturated phosphatidylcholines and either exogenous or endogenous (produced by the enzyme system involving myeloperoxidase (MPO), H2O2, and Cl-) hypochlorite was studied in multilayer liposomes containing oleic, linoleic, and arachidonic acid residues using MALDI-TOF mass spectrometry. At pH 7.4, hypochlorite reacts with the double bond of the oleic acid residue in 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine producing oleic acid chlorohydrin as the main product. Minor amounts of glycols and epoxides were also detected. The main products of the reaction of hypochlorite with 1-stearoyl-2-linoleyl-sn-glycero-3-phosphocholine were mono- and di-chlorohydrins of linoleic acid. The signals of monoglycol, epoxide, and glycol- or epoxide-containing monochlorohydrin derivatives were also present in the mass spectrum. The main products of the reaction of hypochlorite with 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphocholine were lysophosphatidylcholine (1-stearoyl-sn-glycero-3-phosphocholine) and mono-, di-, and trichlorohydrin. Monoglycol and its derivatives containing one or two chlorohydrin groups were also detected. Along with those, carbonyl compounds (aldehyde and acid) formed as a result of double bond breakage in fifth position of arachidonate were detected. Monochlorohydrin was also found when liposomes comprising 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine were incubated in the presence of enzymatic mixture, MPO + H2O2 + Cl-, at pH 6.0. In the absence of the enzyme or either of its substrates (H2O2 or Cl-) or in the presence of the MPO inhibitor (sodium azide) or hypochlorite scavengers (taurine or methionine), monochlorohydrin formation was not observed. These data confirm the suggestion that just the hypochlorite generated in MPO-catalysis provides for chlorohydrin formation. Thus, the use of MALDI-TOF mass spectrometry has shown, along with chlorohydrins, glycols and epoxides as the products of hypochlorite interaction with unsaturated phosphatidylcholines at physiological pH. It was first determined that hypochlorite breaks double bonds in polyunsaturated phosphatidylcholine and also causes lysophosphatidylcholine formation.
3. X-ray grazing incidence diffraction and Langmuir monolayer studies of the interaction of beta-cyclodextrin with model lipid membranes
Jarosław Majewski, Michał Flasiński, Patrycja Dynarowicz-Łatka, Marcin Broniatowski J Colloid Interface Sci . 2010 Aug 15;348(2):511-21. doi: 10.1016/j.jcis.2010.04.086.
The interactions of beta-CD with one component monolayers of cholesterol (chol), 1-stearoyl-sn-glycero-3-phosphocholine (lyso-PC), 1,2-dipalmitpyl-sn-phosphocholine (DPPC), sphingomyelin (SM) and the SM/chol and DPPC/chol mixtures have been investigated by the Langmuir monolayer technique and the synchrotron grazing incidence X-ray diffraction (GIXD). The investigated lipid monolayers have been studied with and without the 10(-3) M solution of beta-CD in the aqueous subphase. The surface pressure-area (pi-A) isotherms and the relaxation of the monolayers (surface pressure-time curves) were monitored. Our experiments reveal that there is not impact of beta-CD on the packing properties of the DPPC monolayers, while the presence of beta-CD in subphase changes the in-plane organization of SM molecules. Monolayers composed of pure chol molecules have been rapidly affected by the presence of the beta-CD in the subphase. Our data show that beta-CD can complex and desorb one-chain phospholipid (lyso-PC) but this process is relatively slow and, as indicated by the GIXD data, beta-CD molecules are present at the air/water interface. Subtraction of cholesterol by the beta-CD from mixed binary systems containing SM/chol (70/30, 50/50 and 30/70 mol ratio) and DPPC/chol (70/30 and 50/50 mol ratio) has also been investigated. Our experiments proved that cholesterol can be removed from the mixed monolayers only when it is unbound. The beta-CD was not capable to distract the monolayers of the SM/chol, forming a stable complex of the 2:1 stoichiometry (as observed in the model lipid raft). Interestingly, at the surface pressure of 30 mN/m also at the molar proportion of 50/50 no cholesterol removal was observed. This was interpreted by relatively strong SM/chol interactions and the tight packing of the mixed monolayer. For model membranes, in which cholesterol was in large excess (SM/chol, 30/70) the beta-CD extraction of cholesterol was observed, and the membrane composition evolves towards the lipid proportion corresponding to the stable complex stoichiometry (SM/chol 2:1).
