Unveiling LOX-1 receptor interplay with nanotopography: mechanotransduction and atherosclerosis onset

Rienzo, Carmine Di; Jacchetti, Emanuela; Cardarelli, Francesco; Bizzarri, Ranieri; Beltram, Fabio; Cecchini, Marco

doi:10.1038/srep01141

Cited by 21 publications

(14 citation statements)

References 57 publications

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“…While COC biocompatibility was already reported3839, nanopatterning by itself could in principle influence cell viability40 by altering cell morphological and functional properties. Experiments were performed at short and medium term: 24 hours and 1 week after seeding.…”

Section: Resultsmentioning

confidence: 99%

Wharton's Jelly human Mesenchymal Stem Cell contact guidance by noisy nanotopographies

Jacchetti

Rienzo

Meucci

et al. 2014

Sci Rep

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The development of biomaterials ensuring proper cell adhesion, polarization, migration and differentiation represents a true enabler for successful tissue-engineering applications. Surface nanostructuring was suggested as a promising method for improving cell-substrate interaction. Here, we study Wharton's Jelly human Mesenchymal Stem Cells (WJ-hMSC) interacting with nanogratings (NGs) having a controlled amount of nanotopographical noise (nTN). Our data demonstrate that unperturbed NGs induce cell polarization, alignment and migration along NG lines. The introduction of nTN dramatically modifies this behavior and leads to a marked loss of cell polarization and directional migration, even at low noise levels. High-resolution focal adhesions (FAs) imaging showed that this behavior is caused by the release of the geometrical vinculum imposed by the NGs to FA shaping and maturation. We argue that highly anisotropic nanopatterned scaffolds can be successfully exploited to drive stem cell migration in regenerative medicine protocols and discuss the impact of scaffold alterations or wear.

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Section: Resultsmentioning

confidence: 99%

Wharton's Jelly human Mesenchymal Stem Cell contact guidance by noisy nanotopographies

Jacchetti

Rienzo

Meucci

et al. 2014

Sci Rep

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“…Mimicking the topographically and biochemically complex environment of the extracellular matrix (ECM) on synthetic substrates such as PVA may help direct specific biological actions such as improving cell adhesion and decreasing platelet activation. For example, mimicking the fibrillar ECM structure in the form of micron-sized gratings on synthetic surfaces has been shown to increase migration and retention under shear stress [15], improve proliferation [16] and retain the atheroprotective phenotype [17] of endothelial cells. Additionally, functionalization of synthetic surfaces with ECM proteins, such as fibronectin [18], vitronectin [19] and laminin [20] were shown to improve endothelial cell attachment.…”

Section: Introductionmentioning

confidence: 99%

In vitro and ex vivo hemocompatibility of off-the-shelf modified poly(vinyl alcohol) vascular grafts

et al. 2015

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Synthetic small diameter vascular grafts with mechanical properties of native arteries, resistance to thrombosis and capacity to stimulate in situ endothelialization are an unmet clinical need. Poly(vinyl alcohol) hydrogel (PVA) is an excellent candidate as a vascular graft due to its tunable mechanical properties. However, the hydrophilicity and bio-inertness of PVA prevents endothelialization in vivo. We hypothesize that the modification of PVA with biomolecules and topographies creates a hemocompatible environment that also enhances bioactivity. PVA modified with fibronectin, RGDS peptide, cyclicRGD (cRGD) peptide, or heparin provided cell-adhesion motifs, which were confirmed by detection of nitrogen through X-ray photoelectron spectroscopy. Protein-and peptide-modified surfaces showed a slight increase in human vascular endothelial cell proliferation over unmodified PVA. With the exception of fibronectin modification, modified surfaces showed in vitro hemocompatibility comparable with unmodified PVA. To further improve bioactivity, cRGD-PVA was combined with gratings and microlens topographies. Combined modifications of 2µm gratings or convex topography and cRGD significantly improved human vascular endothelial cell viability on PVA. In vitro hemocompatibility testing showed that topography on cRGD-PVA did not significantly trigger an increase of platelet adhesion or activation compared with unpatterned PVA. Using the more physiologically relevant ex vivo hemocompatibility testing, all PVA grafts tested showed similar platelet adhesion to ePTFE and significantly lower platelet accumulation compared to collagen-coated ePTFE grafts. The

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“…For instance, it was shown that by performing FCS on differently-sized observation areas one can define an “FCS diffusion law” enlightening hidden features of molecular motion 11,12 . Besides being varied in size, the focal area was also duplicated 13 , moved in space along lines 14–20 or conjugated with fast cameras 21,22 . Using these ‘spatio-temporal’ correlation approaches, relevant biological parameters of several membrane components were quantitatively described on both model membranes and actual biological ones, thus yielding insight into membrane spatial organization.…”

Section: Introductionmentioning

confidence: 99%

From Fast Fluorescence Imaging to Molecular Diffusion Law on Live Cell Membranes in a Commercial Microscope

Rienzo

Gratton

Beltram

et al. 2014

JoVE

Self Cite

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SHORT ABSTRACT Spatial distribution and temporal dynamics of plasma membrane proteins and lipids is a hot topic in biology. Here this issue is addressed by a spatio-temporal image fluctuation analysis that provides conceptually the same physical quantities of single particle tracking, but it uses small molecular labels and standard microscopy setups. LONG ABSTRACT It has become increasingly evident that the spatial distribution and the motion of membrane components like lipids and proteins are key factors in the regulation of many cellular functions. However, due to the fast dynamics and the tiny structures involved, a very high spatio-temporal resolution is required to catch the real behavior of molecules. Here we present the experimental protocol for studying the dynamics of fluorescently-labeled plasma-membrane proteins and lipids in live cells with high spatiotemporal resolution. Notably, this approach doesn’t need to track each molecule, but it calculates population behavior using all molecules in a given region of the membrane. The starting point is a fast imaging of a given region on the membrane. Afterwards, a complete spatio-temporal autocorrelation function is calculated correlating acquired images at increasing time delays, for example each 2, 3, n repetitions. It is possible to demonstrate that the width of the peak of the spatial autocorrelation function increases at increasing time delay as a function of particle movement due to diffusion. Therefore, fitting of the series of autocorrelation functions enables to extract the actual protein mean square displacement from imaging (iMSD), here presented in the form of apparent diffusivity vs average displacement. This yields a quantitative view of the average dynamics of single molecules with nanometer accuracy. By using a GFP-tagged variant of the Transferrin Receptor (TfR) and an ATTO488 labeled 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (PPE) it is possible to observe the spatiotemporal regulation of protein and lipid diffusion on μm-sized membrane regions in the micro-to-milli-second time range.

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Unveiling LOX-1 receptor interplay with nanotopography: mechanotransduction and atherosclerosis onset

Cited by 21 publications

References 57 publications

Wharton's Jelly human Mesenchymal Stem Cell contact guidance by noisy nanotopographies

Wharton's Jelly human Mesenchymal Stem Cell contact guidance by noisy nanotopographies

In vitro and ex vivo hemocompatibility of off-the-shelf modified poly(vinyl alcohol) vascular grafts

From Fast Fluorescence Imaging to Molecular Diffusion Law on Live Cell Membranes in a Commercial Microscope

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