George Altankov - Academia.edu (original) (raw)

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Papers by George Altankov

journal of new results in science, 2017

Mesenchymal stem cells (MSCs) are a promising cell source for cell-based therapies because of the... more Mesenchymal stem cells (MSCs) are a promising cell source for cell-based therapies because of their self-renewal and multi-lineage differentiation potential. Unlike embryonic stem cells adult stem cells are subject of aging processes and the concomitant decline in their function. Age-related changes in MSCs have to be well understood in order to develop clinical techniques and therapeutics based on these cells. In this work we have studied the effect of aging on adhesive behaviour of bone marrow-derived MSC and MG- 63 osteoblastic cells onto three extracellular matrix proteins: fibronectin (FN), vitronectin (VN) and collagen I (Coll I). The results revealed substantial differences in adhesive behaviour of both cell types during 21 days in culture. Bone-marrow derived MSCs decreased significantly their adhesive affinity to all studied proteins after 7th day in culture with further incubation. In contrast, MG-63 cells, demonstrated a stable cell adhesive phenotype with high affinity...

Histology and histopathology, 2008

A series of co-culture experiments between fibroblasts and H-460 human lung carcinoma cells were ... more A series of co-culture experiments between fibroblasts and H-460 human lung carcinoma cells were performed to learn more about the fate of adsorbed type IV collagen (Coll IV). Fibroblasts were able to spatially rearrange Coll IV in a specific linear pattern, similar but not identical to the fibronectin (FN) fibrils. Coll IV partly co-aligns with fibroblast actin cytoskeleton and transiently co-localize with FN, as well as with beta1 and alpha2 integrin clusters, suggesting a cell-dependent process. We further found that this Coll IV reorganization is suppressed in contact with H460 cells. Zymography revealed strongly elevated MMP-2 activity in supernatants of co-cultures, but no activity when fibroblasts or cancer cells were cultured alone. Thus, we provide evidence that reorganization of substrate associated Coll IV is a useful morphological approach for in vitro studies on matrix remodeling activity during tumorigenesis.

Acta biomaterialia, 2018

Extracellular matrix (ECM) proteins are key mediators of cell/material interactions. The surface ... more Extracellular matrix (ECM) proteins are key mediators of cell/material interactions. The surface density and conformation of these proteins adsorbed on the material surface influence cell adhesion and the cellular response. We have previously shown that subtle variations in surface chemistry lead to drastic changes in the conformation of adsorbed fibronectin (FN). On poly(ethyl acrylate) (PEA), FN unfolds and displays domains for cell adhesion and FN-FN interaction, whereas on poly(methyl acrylate) (PMA) - with only one methyl group less - FN remains globular as it is in solution. The effect of the strength of the protein/material interaction in cell response, and its relation to protein density and conformation, has received limited attention so far. In this work, we used FN-functionalized AFM cantilevers to evaluate, via force spectroscopy, the strength of interaction between fibronectin and the underlying polymer which controls FN conformation (PEA and PMA). We found that the str...

Polymer, 2010

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright

Tissue Engineering Part A, 2009

The Journal of cell biology, 1993

To learn more about the possible role of the coated pits endocytic pathway in cell adhesion, we s... more To learn more about the possible role of the coated pits endocytic pathway in cell adhesion, we studied attachment and spreading of fibroblasts whose coated pits were disrupted by depletion of intercellular potassium. Fibroblasts incubated in suspension in potassium-free medium lost 80% of their intracellular potassium within 10 min and showed disrupted coated pits based on fluorescence staining of clathrin. Potassium-depleted cells attached and spread on fibronectin-coated substrata over the same time course (15 min-2 h) as control cells. Unlike controls, however, potassium-depleted fibroblasts attained a radial morphology with circumferentially organized actin filament bundles and were unable to make the transition to a polarized morphology with stress fibers. In the radially spread fibroblasts, fibronectin receptors and vinculin colocalized in focal adhesion sites and appeared to be membrane insertion points for circumferentially arranged actin filament bundles, but these sites w...

Journal of Bioactive and Compatible Polymers, 2011

Fibrinogen (FG) adsorption on surfaces with controlled fraction of —OH groups was investigated wi... more Fibrinogen (FG) adsorption on surfaces with controlled fraction of —OH groups was investigated with AFM and correlated to the initial interaction of primary endothelial cells (HUVEC). The —OH content was tailored making use of a family of copolymers consisting of ethyl acrylate (EA) and hydroxyl ethyl acrylate (HEA) in different ratios. The supramolecular distribution of FG changed from an organized network-like structure on the most hydrophobic surface (—OH 0) to dispersed molecular aggregate one as the fraction of —OH groups increases, indicating a different conformation by the adsorbed protein. The best cellular interaction was observed on the most hydrophobic (—OH 0) surface where FG assembled in a fibrin-like appearance in the absence of any thrombin. Likewise, focal adhesion formation and actin cytoskeleton development was poorer as the fraction of hydroxy groups on the surface was increased. The biological activity of the surface-induced FG network to provide 3D cues in a pot...

Colloids and Surfaces B: Biointerfaces, 2013

Cells assemble fibronectin (FN) into fibrils in a process mediated by integrins. For this process... more Cells assemble fibronectin (FN) into fibrils in a process mediated by integrins. For this process to occur, it is known that the presence of other serum proteins is necessary. However, the individual effect of these proteins on FN fibrillogenesis has not been addressed so far. In this study, the effect of vitronectin (VN), an ECM adhesion protein, on material-driven FN fibrillogenesis and cell-mediated FN reorganization is investigated. Poly(ethyl acrylate), PEA, which has previously shown the ability to induce the organization of FN into well-developed physiological-like networks upon adsorption, was employed as a material substrate. FN adsorption, cell adhesion and cellular FN reorganization in the presence or absence of VN were studied. Both FN surface density, quantified via western blot, and its distribution on PEA surfaces, determined via atomic force microscopy, were altered when FN was adsorbed competitively with VN at certain compositions. Moreover, the presence of VN on the material surfaces enhanced cell-mediated FN reorganization and secretion, in comparison with the process which took place in the presence of serum proteins.

International Journal of Molecular Sciences

Altered Mesenchymal Stem Cells Mechanotransduction from Oxidized Collagen: Morphological and Biophysical Observations, 2023

Extracellular matrix (ECM) provides various mechanical cues that are able to affect the self-rene... more Extracellular matrix (ECM) provides various mechanical cues that are able to affect the self-renewal and differentiation of mesenchymal stem cells (MSC). Little is known, however, how these cues work in a pathological environment, such as acute oxidative stress. To better understand the behavior of human adipose tissue-derived MSC (ADMSC) in such conditions, we provide morphological and quantitative evidence for significantly altered early steps of mechanotransduction when adhering to oxidized collagen (Col-Oxi). These affect both focal adhesion (FA) formation and YAP/TAZ signaling events. Representative morphological images show that ADMSCs spread better within 2 h of adhesion on native collagen (Col), while they tended to round up on Col-Oxi. It also correlates with the lesser development of the actin cytoskeleton and FA formation, confirmed quantitatively by morphometric analysis using ImageJ. As shown by immunofluorescence analysis, oxidation also affected the ratio of cytosolic-to-nuclear YAP/TAZ activity, concentrating in the nucleus for Col while remaining in the cytosol for Col-Oxi, suggesting abrogated signal transduction. Comparative Atomic Force Microscopy (AFM) studies show that native collagen forms relatively coarse aggregates, much thinner with Col-Oxi, possibly reflecting its altered ability to aggregate. On the other hand, the corresponding Young's moduli were only slightly changed, so viscoelastic properties cannot explain the observed biological differences. However, the roughness of the protein layer decreased dramatically, from RRMS equal to 27.95 ± 5.1 nm for Col to 5.51 ± 0.8 nm for Col-Oxi (p < 0.05), which dictates our conclusion that it is the most altered parameter in oxidation. Thus, it appears to be a predominantly topographic response that affects the mechanotransduction of AD-MSCs by oxidized collagen.