Publications by authors named "Sergey Kapishnikov"

16 Publications

  • Page 1 of 1

Micro-CT Analysis of Microgap at a Novel Two-Piece Dental Implant Comprising a Replaceable Sleeve In Vitro.

Int J Oral Maxillofac Implants 2021 May-Jun;36(3):451-459

Purpose: Microcomputed tomography (micro-CT) is a relatively new modality to investigate mechanical deformations. The purpose of this study was to assess the microgap at the implant-sleeve connection of a new two-piece dental implant with a replaceable sleeve.

Materials And Methods: Implants were assembled with 25-degree angulated abutments. Micro-CT was used to assess implant-sleeve connection gaps under the following mechanical conditions: (1) unloading; (2) compressive 10,000 cyclic loading with 400 N; (3) static compressive load of 200 N or 400 N for 24 hours.

Results: The mean gap in the unloaded sample was 2.9 ± 0.9 μm. The mean gap difference after cyclic compressive load was 0.3 ± 0.15 μm, demonstrating a negligible effect for the cyclic loading. Under static compressive load, there was no increase in microgap size at 200 N. At 400 N, a significant (P < .05) increase was noted. While the mean values increased by 1.9 μm, the most pronounced significant increase in mean microgap was noted in the direction of force application (5.1 ± 2.14 μm), while a significant decrease in mean microgap (1.2 ± 1.47 μm) was noted on the opposite side.

Conclusion: The mechanical behavior of the implant-sleeve connection under static and dynamic loads was found to be within the previously reported range of implant dentistry.
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http://dx.doi.org/10.11607/jomi.8563DOI Listing
June 2021

PTPRJ promotes osteoclast maturation and activity by inhibiting Cbl-mediated ubiquitination of NFATc1 in late osteoclastogenesis.

FEBS J 2021 Feb 19. Epub 2021 Feb 19.

Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.

Bone-resorbing osteoclasts (OCLs) are multinucleated phagocytes, whose central roles in regulating bone formation and homeostasis are critical for normal health and development. OCLs are produced from precursor monocytes in a multistage process that includes initial differentiation, cell-cell fusion, and subsequent functional and morphological maturation; the molecular regulation of osteoclastogenesis is not fully understood. Here, we identify the receptor-type protein tyrosine phosphatase PTPRJ as an essential regulator specifically of OCL maturation. Monocytes from PTPRJ-deficient (JKO) mice differentiate and fuse normally, but their maturation into functional OCLs and their ability to degrade bone are severely inhibited. In agreement, mice lacking PTPRJ throughout their bodies or only in OCLs exhibit increased bone mass due to reduced OCL-mediated bone resorption. We further show that PTPRJ promotes OCL maturation by dephosphorylating the M-CSF receptor (M-CSFR) and Cbl, thus reducing the ubiquitination and degradation of the key osteoclastogenic transcription factor NFATc1. Loss of PTPRJ increases ubiquitination of NFATc1 and reduces its amounts at later stages of osteoclastogenesis, thereby inhibiting OCL maturation. PTPRJ thus fulfills an essential and cell-autonomous role in promoting OCL maturation by balancing between the pro- and anti-osteoclastogenic activities of the M-CSFR and maintaining NFATc1 expression during late osteoclastogenesis.
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http://dx.doi.org/10.1111/febs.15778DOI Listing
February 2021

Malaria Pigment Crystals: The Achilles' Heel of the Malaria Parasite.

ChemMedChem 2021 May 19;16(10):1515-1532. Epub 2021 Mar 19.

Dept. of Molecular Chemistry and Materials Science, Weizmann Institute of Science, Rehovot, 7610001, Israel.

The biogenic formation of hemozoin crystals, a crucial process in heme detoxification by the malaria parasite, is reviewed as an antimalarial drug target. We first focus on the in-vivo formation of hemozoin. A model is presented, based on native-contrast 3D imaging obtained by X-ray and electron microscopy, that hemozoin nucleates at the inner membrane leaflet of the parasitic digestive vacuole, and grows in the adjacent aqueous medium. Having observed quantities of hemoglobin and hemozoin in the digestive vacuole, we present a model that heme liberation from hemoglobin and hemozoin formation is an assembly-line process. The crystallization is preceded by reaction between heme monomers yielding hematin dimers involving fewer types of isomers than in synthetic hemozoin; this is indicative of protein-induced dimerization. Models of antimalarial drugs binding onto hemozoin surfaces are reviewed. This is followed by a description of bromoquine, a chloroquine drug analogue, capping a significant fraction of hemozoin surfaces within the digestive vacuole and accumulation of the drug, presumably a bromoquine-hematin complex, at the vacuole's membrane.
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http://dx.doi.org/10.1002/cmdc.202000895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252759PMC
May 2021

Niemann Pick C2 protein enables cholesterol transfer from endo-lysosomes to the plasma membrane for efflux by shedding of extracellular vesicles.

Chem Phys Lipids 2021 03 7;235:105047. Epub 2021 Jan 7.

Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230, Odense M, Denmark. Electronic address:

The Niemann-Pick C2 protein (NPC2) is a sterol transfer protein in the lumen of late endosomes and lysosomes (LE/LYSs). Absence of functional NPC2 leads to endo-lysosomal buildup of cholesterol and other lipids. How NPC2's known capacity to transport cholesterol between model membranes is linked to its function in living cells is not known. Using quantitative live-cell imaging combined with modeling of the efflux kinetics, we show that NPC2-deficient human fibroblasts can export the cholesterol analog dehydroergosterol (DHE) from LE/LYSs. Internalized NPC2 accelerated sterol efflux extensively, accompanied by reallocation of LE/LYSs containing fluorescent NPC2 and DHE to the cell periphery. Using quantitative fluorescence loss in photobleaching of TopFluor-cholesterol (TF-Chol), we estimate a residence time for a rapidly exchanging sterol pool in LE/LYSs localized in close proximity to the plasma membrane (PM), of less than one min and observed non-vesicular sterol exchange between LE/LYSs and the PM. Excess sterol was released from the PM by shedding of cholesterol-rich vesicles. The ultrastructure of such vesicles was analyzed by combined fluorescence and cryo soft X-ray tomography (SXT), revealing that they can contain lysosomal cargo and intraluminal vesicles. Treating cells with apoprotein A1 and with nuclear receptor liver X-receptor (LXR) agonists to upregulate expression of ABC transporters enhanced cholesterol efflux from the PM, at least partly by accelerating vesicle release. We conclude that NPC2 inside LE/LYSs facilitates non-vesicular sterol exchange with the PM for subsequent sterol efflux to acceptor proteins and for shedding of sterol-rich vesicles from the cell surface.
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http://dx.doi.org/10.1016/j.chemphyslip.2020.105047DOI Listing
March 2021

The need to freeze-Dehydration during specimen preparation for electron microscopy collapses the endothelial glycocalyx regardless of fixation method.

Microcirculation 2020 10 26;27(7):e12643. Epub 2020 Jul 26.

Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.

Objective: The endothelial glycocalyx covers the luminal surface of the endothelium and plays key roles in vascular function. Despite its biological importance, ideal visualization techniques are lacking. The current study aimed to improve the preservation and subsequent imaging quality of the endothelial glycocalyx.

Methods: In mice, the endothelial glycocalyx was contrasted with a mixture of lanthanum and dysprosium (LaDy). Standard chemical fixation was compared with high-pressure frozen specimens processed with freeze substitution. Also, isolated brain microvessels and cultured endothelial cells were high-pressure frozen and by transmission soft x-rays, imaged under cryogenic conditions.

Results: The endothelial glycocalyx was in some tissues significantly more voluminous from chemically fixed specimens compared with high-pressure frozen specimens. LaDy labeling introduced excessive absorption contrast, which impeded glycocalyx measurements in isolated brain microvessels when using transmission soft x-rays. In non-contrasted vessels, the glycocalyx was not resolved. LaDy-contrasted, cultured brain endothelial cells allowed to assess glycocalyx volume in vitro.

Conclusions: Both chemical and cryogenic fixation followed by dehydration lead to substantial collapse of the glycocalyx. Cryogenic fixation without freeze substitution could be a way forward although transmission soft x-ray tomography based solely on amplitude contrast seems unsuitable.
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http://dx.doi.org/10.1111/micc.12643DOI Listing
October 2020

Strong, tough and bio-degradable polymer-based 3D-ink for fused filament fabrication (FFF) using WS nanotubes.

Sci Rep 2020 06 1;10(1):8892. Epub 2020 Jun 1.

Department of Materials Science and Engineering, Faculty of Engineering, Tel-Aviv University, Ramat Aviv, Tel Aviv, 6997801, Israel.

WS inorganic nanotubes (WS-NT) have been incorporated into Polylactic Acid (PLA) by melt mixing to create a bio-degradable, mechanically reinforced nanocomposite filament. The filament was then processed by Fused Filament Fabrication (FFF) 3D-printer, and the morphology and characteristics before and after printing were compared. We found that addition of WS-NT to PLA by extrusion mixing increases the elastic modulus, yield strength and strain-at-failure by 20%, 23% and 35%, respectively. Moreover, we found that the printing process itself improves the dispersion of WS-NT within the PLA filament, and does not require changing of the printing parameters compared to pure PLA. The results demonstrate the advantage of WS-NT as reinforcement specifically in 3D-printable polymers, over more traditional nano-reinforcements such as graphene and carbon nanotubes. WS-NT based 3D-printable nanocomposites can be used for variety of applications from custom-made biodegradable scaffold of soft implants such as cartilage-based organs and biodegradable soft stents to the more general easy-to-apply nano-reinforced polymers.
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http://dx.doi.org/10.1038/s41598-020-65861-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264276PMC
June 2020

Cells Undergo Major Changes in the Quantity of Cytoplasmic Organelles after Uptake of Gold Nanoparticles with Biologically Relevant Surface Coatings.

ACS Nano 2020 02 28;14(2):2248-2264. Epub 2020 Jan 28.

Helmholtz Zentrum Berlin für Materialien und Energie GmbH , Wilhelm-Conrad-Röntgen Campus, Albert-Einstein-Str. 15 , 12489 Berlin , Germany.

Here, we use cryo soft X-ray tomography (cryo-SXT), which delivers 3D ultrastructural volumes of intact cells without chemical fixation or staining, to gain insight about nanoparticle uptake for nanomedicine. We initially used dendritic polyglycerol sulfate (dPGS) with potential diagnostic and therapeutic applications in inflammation. Although dPGS-coated gold nanoparticle (dPGS-AuNP) uptake followed a conventional endocytic/degradative pathway in human lung epithelial cell lines (A549), with cryo-SXT, we detected ∼5% of dPGS-AuNPs in the cytoplasm, a level undetectable by confocal light microscopy. We also observed ∼5% of dPGS-AuNPs in a rarely identified subcellular site, namely, lipid droplets, which are important for cellular energy metabolism. Finally, we also found substantial changes in the quantity of cytoplasmic organelles upon dPGS-AuNP uptake over the 1-6 h incubation period; the number of small vesicles and mitochondria significantly increased, and the number of multivesicular bodies and the number and volume of lipid droplets significantly decreased. Although nearly all organelle numbers at 6 h were still significantly different from controls, most appeared to be returning to normal levels. To test for generality, we also examined cells after uptake of gold nanoparticles coated with a different agent, polyethylenimine (PEI), used for nucleic acid delivery. PEI nanoparticles did not enter lipid droplets, but they induced similar, albeit less pronounced, changes in the quantity of cytoplasmic organelles. We confirmed these changes in organelle quantities for both nanoparticle coatings by confocal fluorescence microscopy. We suggest this cytoplasmic remodeling could reflect a more common cellular response to coated gold nanoparticle uptake.
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http://dx.doi.org/10.1021/acsnano.9b09264DOI Listing
February 2020

Mode of action of quinoline antimalarial drugs in red blood cells infected by revealed in vivo.

Proc Natl Acad Sci U S A 2019 11 28;116(46):22946-22952. Epub 2019 Oct 28.

Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark.

The most widely used antimalarial drugs belong to the quinoline family. Their mode of action has not been characterized at the molecular level in vivo. We report the in vivo mode of action of a bromo analog of the drug chloroquine in rapidly frozen -infected red blood cells. The parasite digests hemoglobin, liberating the heme as a byproduct, toxic to the parasite. It is detoxified by crystallization into inert hemozoin within the parasitic digestive vacuole. By mapping such infected red blood cells with nondestructive X-ray microscopy, we observe that bromoquine caps hemozoin crystals. The measured crystal surface coverage is sufficient to inhibit further hemozoin crystal growth, thereby sabotaging heme detoxification. Moreover, we find that bromoquine accumulates in the digestive vacuole, reaching submillimolar concentration, 1,000-fold more than that of the drug in the culture medium. Such a dramatic increase in bromoquine concentration enhances the drug's efficiency in depriving heme from docking onto the hemozoin crystal surface. Based on direct observation of bromoquine distribution in the digestive vacuole and at its membrane surface, we deduce that the excess bromoquine forms a complex with the remaining heme deprived from crystallization. This complex is driven toward the digestive vacuole membrane, increasing the chances of membrane puncture and spillage of heme into the interior of the parasite.
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http://dx.doi.org/10.1073/pnas.1910123116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859308PMC
November 2019

Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography.

Sci Rep 2017 08 8;7(1):7610. Epub 2017 Aug 8.

Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, 76100, Israel.

A key drug target for malaria has been the detoxification pathway of the iron-containing molecule heme, which is the toxic byproduct of hemoglobin digestion. The cornerstone of heme detoxification is its sequestration into hemozoin crystals, but how this occurs remains uncertain. We report new results of in vivo rate of heme crystallization in the malaria parasite, based on a new technique to measure element-specific concentrations at defined locations in cell ultrastructure. Specifically, a high resolution correlative combination of cryo soft X-ray tomography has been developed to obtain 3D parasite ultrastructure with cryo X-ray fluorescence microscopy to measure heme concentrations. Our results are consistent with a model for crystallization via the heme detoxification protein. Our measurements also demonstrate the presence of considerable amounts of non-crystalline heme in the digestive vacuole, which we show is most likely contained in hemoglobin. These results suggest a tight coupling between hemoglobin digestion and heme crystallization, highlighting a new link in the crystallization pathway for drug development.
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http://dx.doi.org/10.1038/s41598-017-06650-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548722PMC
August 2017

Development of Correlative Cryo-soft X-ray Tomography and Stochastic Reconstruction Microscopy. A Study of Cholesterol Crystal Early Formation in Cells.

J Am Chem Soc 2016 11 8;138(45):14931-14940. Epub 2016 Nov 8.

Experimental Atherosclerosis Section, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland 20892-1422, United States.

We have developed a high resolution correlative method involving cryo-soft X-ray tomography (cryo-SXT) and stochastic optical reconstruction microscopy (STORM), which provides information in three dimensions on large cellular volumes at 70 nm resolution. Cryo-SXT morphologically identified and localized aggregations of carbon-rich materials. STORM identified specific markers on the desired epitopes, enabling colocalization between the identified objects, in this case cholesterol crystals, and the cellular environment. The samples were studied under ambient and cryogenic conditions without dehydration or heavy metal staining. The early events of cholesterol crystal development were investigated in relation to atherosclerosis, using as model macrophage cell cultures enriched with LDL particles. Atherosclerotic plaques build up in arteries in a slow process involving cholesterol crystal accumulation. Cholesterol crystal deposition is a crucial stage in the pathological cascade. Our results show that cholesterol crystals can be identified and imaged at a very early stage on the cell plasma membrane and in intracellular locations. This technique can in principle be applied to other biological samples where specific molecular identification is required in conjunction with high resolution 3D-imaging.
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http://dx.doi.org/10.1021/jacs.6b07584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530486PMC
November 2016

Digestive vacuole membrane in Plasmodium falciparum-infected erythrocytes: relevance to templated nucleation of hemozoin.

Langmuir 2013 Nov 15;29(47):14595-602. Epub 2013 Nov 15.

Department of Materials and Interfaces, Weizmann Institute of Science , Rehovot 76100, Israel.

Crystallization of the malaria pigment hemozoin sequesters the toxic heme byproduct of hemoglobin digestion in Plasmodium -infected red blood cells (RBCs). Recently, we applied electron and X-ray imaging and diffraction methods to elucidate this process. We observed crystals oriented with their {100} faces at the inner membrane surface of the digestive vacuole (DV) of Plasmodium falciparum in parasitized RBCs. Modeling of the soft X-ray tomographic (SXT) images of a trophozoite-stage parasite indicated a 4-16 nm DV membrane thickness, suggesting a possible role for lipid multilayers. Here, we reanalyzed the trophozoite SXT images quantitatively via X-ray absorption to map the DV membrane thickness. Making use of the chemical structure and crystal density of the lipid, we found, predominantly, a bilayer 4.2 nm thick, and the remainder was interpreted as patches ∼8 nm thick. Image analysis of electron micrographs also yielded a 4-5 nm DV membrane thickness. The DV lipid membrane is thus mainly a bilayer, so induced hemozoin nucleation occurs primarily via the inner of the membrane's two leaflets. We argue that such a leaflet embodying mono- and di-acyl lipids with appropriate OH or NH bearing head groups may catalyse hemozoin nucleation by stereochemical and lattice match to the {100} crystal face, involving a two-dimensional nucleation aggregate of ∼100 molecules.
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http://dx.doi.org/10.1021/la402545cDOI Listing
November 2013

Vitrification of thick samples for soft X-ray cryo-tomography by high pressure freezing.

J Struct Biol 2013 Jan 16;181(1):77-81. Epub 2012 Oct 16.

Dept. of Materials and Interfaces, Weizmann Institute of Science, Rehovot 76100, Israel.

Soft X-ray cryo-microscopy (cryo-XT) offers an ideal complement to electron cryo-microscopy (cryo-EM). Cryo-XT is applicable to samples more than an order of magnitude thicker than cryo-EM, albeit at a more modest resolution of tens of nanometers. Furthermore, the natural contrast obtained in the "water-window" by differential absorption by organic matter vs water yields detailed images of organelles, membranes, protein complexes, and other cellular components. Cryo-XT is thus ideally suited for tomography of eukaryotic cells. The increase in sample thickness places more stringent demands on sample preparation, however. The standard method for cryo-EM, i.e., plunging to a cryogenic fluid such as liquid ethane, is no longer ideally suited to obtain vitrification of thick samples for cryo-XT. High pressure freezing is an alternative approach, most closely associated with freeze-substitution and embedding, or with electron cryo-microscopy of vitreous sections (CEMOVIS). We show here that high pressure freezing can be adapted to soft X-ray tomography of whole vitrified samples, yielding a highly reliable method that avoids crystallization artifacts and potentially offers improved imaging conditions in samples not amenable to plunge-freezing.
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http://dx.doi.org/10.1016/j.jsb.2012.10.005DOI Listing
January 2013

Oriented nucleation of hemozoin at the digestive vacuole membrane in Plasmodium falciparum.

Proc Natl Acad Sci U S A 2012 Jul 28;109(28):11188-93. Epub 2012 Jun 28.

Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot 76100, Israel.

Heme detoxification is a critical step in the life cycle of malaria-causing parasites, achieved by crystallization into physiologically insoluble hemozoin. The mode of nucleation has profound implications for understanding the mechanism of action of antimalarial drugs that inhibit hemozoin growth. Several lines of evidence point to involvement of acylglycerol lipids in the nucleation process. Hemozoin crystals have been reported to form within lipid nanospheres; alternatively, it has been found in vitro that they are nucleated at an acylglycerol lipid-water interface. We have applied cryogenic soft X-ray tomography and three-dimensional electron microscopy to address the location and orientation of hemozoin crystals within the digestive vacuole (DV), as a signature of their nucleation and growth processes. Cryogenic soft X-ray tomography in the "water window" is particularly advantageous because contrast generation is based inherently on atomic absorption. We find that hemozoin nucleation occurs at the DV inner membrane, with crystallization occurring in the aqueous rather than lipid phase. The crystal morphology indicates a common {100} orientation facing the membrane as expected of templated nucleation. This is consistent with conclusions reached by X-ray fluorescence and diffraction in a companion work. Uniform dark spheres observed in the parasite were identified as hemoglobin transport vesicles. Their analysis supports a model of hemozoin nucleation primarily in the DV. Modeling of the contrast at the DV membrane indicates a 4-nm thickness with patches about three times thicker, possibly implicated in the nucleation.
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http://dx.doi.org/10.1073/pnas.1118120109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396484PMC
July 2012

Aligned hemozoin crystals in curved clusters in malarial red blood cells revealed by nanoprobe X-ray Fe fluorescence and diffraction.

Proc Natl Acad Sci U S A 2012 Jul 25;109(28):11184-7. Epub 2012 Jun 25.

Department of Materials and Interfaces, The Weizmann Institute of Science, Rehovot 76100, Israel.

The human malaria parasite Plasmodium falciparum detoxifies the heme byproduct of hemoglobin digestion in infected red blood cells by sequestration into submicron-sized hemozoin crystals. The crystal is composed of heme units interlinked to form cyclic dimers via reciprocal Fe─O (propionate) bonds. Templated hemozoin nucleation was envisaged to explain a classic observation by electron microscopy of a cluster of aligned hemozoin crystals within the parasite digestive vacuole. This dovetails with evidence that acylglycerol lipids are involved in hemozoin nucleation in vivo, and nucleation of β-hematin, the synthetic analogue of hemozoin, was consistently induced at an acylglycerol-water interface via their {100} crystal faces. In order to ascertain the nature of hemozoin nucleation in vivo, we probed the mutual orientations of hemozoin crystals in situ within RBCs using synchrotron-based X-ray nanoprobe Fe fluorescence and diffraction. The X-ray patterns indicated the presence of hemozoin clusters, each comprising several crystals aligned along their needle c axes and exposing {100} side faces to an approximately cylindrical surface, suggestive of nucleation via a common lipid layer. This experimental finding, and the associated nucleation model, are difficult to reconcile with recent reports of hemozoin formation within lipid droplets in the digestive vacuole. The diffraction results are verified by a study of the nucleation process using emerging tools of three-dimensional cellular microscopy, described in the companion paper.
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http://dx.doi.org/10.1073/pnas.1118134109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396539PMC
July 2012

The antimalarial ferroquine: role of the metal and intramolecular hydrogen bond in activity and resistance.

ACS Chem Biol 2011 Mar 7;6(3):275-87. Epub 2011 Jan 7.

Université de Lille, Unité de Catalyse et Chimie du Solide - UMR CNRS, ENSCL, Villeneuve d'Ascq, France.

Inhibition of hemozoin biocrystallization is considered the main mechanism of action of 4-aminoquinoline antimalarials including chloroquine (CQ) but cannot fully explain the activity of ferroquine (FQ) which has been related to redox properties and intramolecular hydrogen bonding. Analogues of FQ, methylferroquine (Me-FQ), ruthenoquine (RQ), and methylruthenoquine (Me-RQ), were prepared. Combination of physicochemical and molecular modeling methods showed that FQ and RQ favor intramolecular hydrogen bonding between the 4-aminoquinoline NH group and the terminal amino group in the absence of water, suggesting that this structure may enhance its passage through the membrane. This was further supported by the use of Me-FQ and Me-RQ where the intramolecular hydrogen bond cannot be formed. Docking studies suggest that FQ can interact specifically with the {0,0,1} and {1,0,0} faces of hemozoin, blocking crystal growth. With respect to the structure-activity relationship, the antimalarial activity on 15 different P. falciparum strains showed that the activity of FQ and RQ were correlated with each other but not with CQ, confirming lack of cross resistance. Conversely, Me-FQ and Me-RQ showed significant cross-resistance with CQ. Mutations or copy number of pfcrt, pfmrp, pfmdr1, pfmdr2, or pfnhe-1 did not exhibit significant correlations with the IC(50) of FQ or RQ. We next showed that FQ and Me-FQ were able to generate hydroxyl radicals, whereas RQ and me-RQ did not. Ultrastructural studies revealed that FQ and Me-FQ but not RQ or Me-RQ break down the parasite digestive vacuole membrane, which could be related to the ability of the former to generate hydroxyl radicals.
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http://dx.doi.org/10.1021/cb100322vDOI Listing
March 2011

Laser-induced aligned self-assembly on water surfaces.

J Chem Phys 2009 Apr;130(14):144704

Department of Materials and Interfaces, The Weizmann Institute of Science, Rehovot 76100, Israel.

The key to functionalize of engineered molecularly nanometer thick films lies in the ability to reproducibly control their structure. A number of factors influence the film morphology of self-assembled films on solid or liquid surfaces, such as the structure of the molecules/particles, wetting, solvent hydrodynamics, and evaporation. An important example is the deposition of amphiphilic molecules from a volatile solution, self-assembled onto a water surface at monolayer coverage. Upon evaporation, a myriad of microscopic two-dimensional (2D) crystallites forms a ruptured film lying in random orientation on the surface, resulting in "2D powders." Here we present a general technique, employing linearly polarized laser pulses and varying solvent composition to influence the assembly of molecules such as poly-benzyl-L-glutamate and alamethicin on water surfaces, resulting in ultrathin molecular films with aligned regions that point in the same direction, though macroscopically separated. The experimental results are tentatively explained by a mechanism that is based on excluded volume forces and "kick model" for the effect of laser pulses to induce molecular rotation that eventually results in an aligned pattern when the system is at a collective state.
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http://dx.doi.org/10.1063/1.3108540DOI Listing
April 2009
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