scholarly journals Hybrid gelation processes in enzymatically gelled gelatin: impact on nanostructure, macroscopic properties and cellular response

Soft Matter ◽  
2013 ◽  
Vol 9 (29) ◽  
pp. 6986-6999 ◽  
Author(s):  
Franziska Bode ◽  
Marcelo Alves da Silva ◽  
Paul Smith ◽  
Christian D. Lorenz ◽  
Seth McCullen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cellular Response ◽  
Cross Linking ◽  
Cluster Growth ◽  
Macroscopic Properties ◽  
Physical Gelation ◽  
Triple Helices

Enzymatic cross-linking of gelatin (left) proceeds through cluster growth (red); when combined with physical gelation, clusters are constrained by triple-helices (black), yielding a more ordered and efficient network, favouring cell proliferation.

scholarly journals The Interactome of Cancer-Related Lysyl Oxidase and Lysyl Oxidase-Like Proteins

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 71
Author(s):  
Sylvain D. Vallet ◽  
Coline Berthollier ◽  
Romain Salza ◽  
Laurent Muller ◽  
Sylvie Ricard-Blum
Keyword(s):  
Protein Folding ◽  
Cancer Progression ◽  
Cellular Response ◽  
Lysyl Oxidase ◽  
Chaperone Activity ◽  
Cross Linking ◽  
Binding Assays ◽  
Vessel Development ◽  
New Interactions

The members of the lysyl oxidase (LOX) family are amine oxidases, which initiate the covalent cross-linking of the extracellular matrix (ECM), regulate ECM stiffness, and contribute to cancer progression. The aim of this study was to build the first draft of the interactome of the five members of the LOX family in order to determine its molecular functions, the biological and signaling pathways mediating these functions, the biological processes it is involved in, and if and how it is rewired in cancer. In vitro binding assays, based on surface plasmon resonance and bio-layer interferometry, combined with queries of interaction databases and interaction datasets, were used to retrieve interaction data. The interactome was then analyzed using computational tools. We identified 31 new interactions and 14 new partners of LOXL2, including the α5β1 integrin, and built an interactome comprising 320 proteins, 5 glycosaminoglycans, and 399 interactions. This network participates in ECM organization, degradation and cross-linking, cell-ECM interactions mediated by non-integrin and integrin receptors, protein folding and chaperone activity, organ and blood vessel development, cellular response to stress, and signal transduction. We showed that this network is rewired in colorectal carcinoma, leading to a switch from ECM organization to protein folding and chaperone activity.

scholarly journals Cellular Orientation on Repeatedly Stretching Gelatin Hydrogels with Supramolecular Cross-Linkers

Polymers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2095
Author(s):  
Dae Hoon Lee ◽  
Yoshinori Arisaka ◽  
Asato Tonegawa ◽  
Tae Woong Kang ◽  
Atsushi Tamura ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Chemical Composition ◽  
Cellular Response ◽  
Linear Polymer ◽  
Cross Linking ◽  
Adherent Cells ◽  
Cell Cultivation ◽  
Supramolecular Compound ◽  
Synthetic Materials ◽  
Cyclic Molecules

The cytocompatibility of biological and synthetic materials is an important issue for biomaterials. Gelatin hydrogels are used as biomaterials because of their biodegradability. We have previously reported that the mechanical properties of gelatin hydrogels are improved by cross-linking with polyrotaxanes, a supramolecular compound composed of many cyclic molecules threaded with a linear polymer. In this study, the ability of gelatin hydrogels cross-linked by polyrotaxanes (polyrotaxane–gelatin hydrogels) for cell cultivation was investigated. Because the amount of polyrotaxanes used for gelatin fabrication is very small, the chemical composition was barely altered. The structure and wettability of these hydrogels are also the same as those of conventional hydrogels. Fibroblasts adhered on polyrotaxane–gelatin hydrogels and conventional hydrogels without any reduction or apoptosis of adherent cells. From these results, the polyrotaxane–gelatin hydrogels have the potential to improve the mechanical properties of gelatin without affecting cytocompatibility. Interestingly, when cells were cultured on polyrotaxane–gelatin hydrogels after repeated stress deformation, the cells were spontaneously oriented to the stretching direction. This cellular response was not observed on conventional hydrogels. These results suggest that the use of a polyrotaxane cross-linking agent can not only improve the strength of hydrogels but can also contribute to controlling reorientation of the gelatin.

Hyaluronic Acid Hydrogel Particles Obtained Using Liposomes as Templates

2021 ◽  
Vol 7 (1) ◽  
pp. 7
Author(s):  
Irene Abelenda Núñez ◽  
Ramón G. Rubio ◽  
Francisco Ortega ◽  
Eduardo Guzmán
Keyword(s):  
Cell Proliferation ◽  
Cross Linking ◽  
Hydrogel Particles ◽  
Cell Proliferation And Migration ◽  
Different Types ◽  
And Migration ◽  
Tissue Matrix ◽  
Hyaluronic Acid Hydrogel ◽  
3D Networks ◽  
Proliferation And Migration

Hydrogels (HG) are 3D networks of hydrophilic macromolecules linked by different “cross-linking points”, which have as a main advantage their capacity for the adsorption of large amounts of water without any apparent dissolution. This allows hydrogels to undergo reversible swelling–shrinking processes upon the modification of the environmental conditions (pH, ionic strength or temperature). This stimuli-responsiveness and their ability for entrapping in their interior different types of molecules makes hydrogels suitable platforms for drug delivery applications. Furthermore, HGs exhibit certain similarities to the extracellular tissue matrix and can be used as a support for cell proliferation and migration.

scholarly journals Active targeting of nanoparticles: An innovative technology for drug delivery in cancer therapeutics

2019 ◽  
Vol 9 (1-s) ◽  
pp. 408-415 ◽  
Author(s):  
Rupalben Kaushalkumar Jani ◽  
Gohil Krupa
Keyword(s):  
Drug Delivery ◽  
Cell Proliferation ◽  
Cancer Therapy ◽  
Targeted Delivery ◽  
Cancer Therapeutics ◽  
Active Targeting ◽  
Innovative Technology ◽  
Cross Linking ◽  
Uncontrolled Cell Proliferation ◽  
Insight Into

In nanomedicines, currently a wide array of reported nanoparticle systems is being explored by targeting schemes which suggests great potential of targeted delivery to revolutionize cancer therapeutics. This review  gives insight into recent  challenges in modification of nanoparticle systems for enhanced cancer therapy  acknowledged by researchers to date and also outlines different major targeting strategies of nanoparticle systems that have been utilized for the delivery of therapeutics or imaging agents, targeting ligand and cross-linking agent to cancer  which was divided into three sections: 1) Angiogenesis associated targeting, 2) Uncontrolled cell proliferation targeting and 3) Tumor cell targeting. Keywords: nanoparticles, tumor cells, active targeting, targeting strategies, targeting ligands

scholarly journals Enhanced Cell Proliferation and Osteogenesis Differentiation through a Combined Treatment of Poly-L-Lysine-Coated PLGA/Graphene Oxide Hybrid Fiber Matrices and Electrical Stimulation

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Jiaqi Zhu ◽  
Zhiping Qi ◽  
Changjun Zheng ◽  
Pan Xue ◽  
Chuan Fu ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Proliferation ◽  
Graphene Oxide ◽  
Electrical Stimulation ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Cellular Response ◽  
Hybrid Fiber ◽  
Fiber Matrices

Bone tissue engineering scaffold provides an effective treatment for bone defect repair. Biodegradable bone scaffold made of various synthetic and natural materials can be used as bone substitutes and grafts for defect site, which has great potential to support bone regeneration. Regulation of cell-scaffold material interactions is an important factor for modulating the cellular activity in bone tissue engineering scaffold applications. Thus, the hydrophilic, mechanical, and chemical properties of scaffold materials directly affect the results of bone regeneration and functional recovery. In this study, a poly-L-lysine (PLL) surface-modified poly(lactic-co-glycolic acid) (PLGA)/graphene oxide (GO) (PLL-PLGA/GO) hybrid fiber matrix was fabricated for bone tissue regeneration. Characterization of the resultant hybrid fiber matrices was done using scanning electron microscopy (SEM), contact angle, and a material testing machine. According to the results obtained from the test above, the PLL-PLGA/GO hybrid fiber matrices exhibited high wettability and mechanical strength. The special surface characteristics of PLL-PLGA/GO hybrid fiber matrices were more beneficial for protein adsorption and inhibit the proliferation of pathogens. Moreover, the enhanced regulation of MC3T3-E1 cell proliferation and differentiation was observed, when the resultant hybrid fiber matrices were combined with electrical stimulation (ES). The cellular response of MC3T3-E1 cells including cell adhesion, proliferation, alkaline phosphatase (ALP) activity, calcium deposition, and osteogenesis-related gene expression was significantly enhanced with the synergistic effect of resultant hybrid fiber matrices and ES. These data indicate that the PLL-PLGA/GO hybrid fiber matrices supported the cellular response in terms of cell proliferation and osteogenesis differentiation in the presence of electrical stimulation, which could be a potential treatment for bone defect.

scholarly journals A Profibrotic Phenotype in Naïve and in Fibrotic Lung Myofibroblasts Is Governed by Modulations in Thy-1 Expression and Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Pazit Y. Cohen ◽  
Raphael Breuer ◽  
Shulamit B. Wallach-Dayan
Keyword(s):  
Cell Proliferation ◽  
Genetic Manipulation ◽  
Cell Mass ◽  
Angiotensin Receptors ◽  
Cross Linking ◽  
Collagen Deposition ◽  
Wild Type ◽  
Abnormal Accumulation ◽  
Free Environment ◽  
Deficient Mice

Lung fibrosis is characterized by abnormal accumulation of Thy-deficient fibroblasts in the interstitium of the alveolar space. We have previously shown in bleomycin-treated chimeric Thy1-deficient mice with wild-type lymphocytes that Thy1-deficient fibroblasts accumulate and promote fibrosis and an “inflammation-free” environment. Here, we aimed to identify the critical effects of Thy1, or the absence of Thy1, in lung myofibroblast profibrotic functions, particularly proliferation and collagen deposition. Using specific Thy1 siRNA in Thy1-positive cells, Thy1 knockout cells, Thy1 cDNA expression vector in Thy1-deficient cells, and Thy1 cross-linking, we evaluated cell proliferation (assessed by cell mass and BrdU uptake), differentiation (using immunofluorescence), and collagen deposition (using Sircol assay). We found that myofibroblast Thy1 cross-linking and genetic manipulation modulate cell proliferation and expression of Fgf (fibroblast growth factor) and Angtl (angiotensin) receptors (using qPCR) that are involved in myofibroblast proliferation, differentiation, and collagen deposition. In conclusion, lung myofibroblast downregulation of Thy1 expression is critical to increase proliferation, differentiation, and collagen deposition.

The Novel Bispecific Diabody αCD40/αCD28 Strengthens Leukemic Dendritic Cell Induced T Cell Reactivity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3710-3710
Author(s):  
Ilse Houtenbos ◽  
Saskia J.A.M. Santegoets ◽  
Theresia M. Westers ◽  
Quinten Waisfisz ◽  
Sergey Kipriyanov ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cd8 T Cells ◽  
Cluster Formation ◽  
T Cell Proliferation ◽  
Cross Linking ◽  
Bispecific Diabody ◽  
Control Protein

Abstract Dendritic cell (DC)-based immunotherapy faces new challenges since efficacy of DC vaccines in clinical trials has been inconsistent. Strategies to improve immune responses induced by DC are currently being explored. We have recently shown the feasibility of generating fully functional DC from Acute Myeloid Leukemic (AML) blasts, but with varying expression levels of the important costimulatory molecule CD86. To overcome this variability, we developed a novel bispecific diabody (BsDb) simultaneously and agonistically targeting CD40 on AML-DC and CD28 on naïve T cells. Beside optimization of CD28-mediated signaling, the resulting cellular cross-linking was also hypothesized to increase the strength and duration of T cell/AML-DC interactions, thus increasing T cell responsiveness to AML antigens. Indeed the αCD40/αCD28-bispecific diabody provokes increased T cell-DC cluster formation as assessed by light microscopy. Significant increased cluster formation was observed when T cells and AML-DC were cocultured in presence of the BsDb as compared to T cells incubated with a control protein (46%±2 versus 22%±1 respectively, p<0.05). Prior incubation of T cells and/or AML-DC with CD28 or CD40, respectively, completely prevented cluster formation in presence of the BsDb indicating specific binding of the BsDb to CD40 and CD28. The αCD40/αCD28 BsDb significantly increases T cell proliferation induced by AML-DC as compared to the unstimulated cocultures, in a dose dependent manner, as evaluated by mixed lymphocyte reactions (fold increased T cell proliferation of cocultures stimulated with BsDb as compared to unstimulated cocultures:170%±12, p<0.05). In addition, BsDb is capable of DC maturation induction as shown by significant increased mean fluorescence index (MFI) of the maturation markers CD80 (MFI of AML-DC cultured in presence of control protein vs AML-DC cultured in presence of BsDb: 22±5 vs 12±3, p<0.05) and CD83 (4±1 vs 1.5±0.5, p<0.05). In order to determine the effect of aCD40/aCD28-bispecific diabody-mediated cross-linking of AML-derived DC and CD8+ T cells on the induction efficiency of tumor-specific CTL, AML-DC derived from the HLA-A2+ AML cell line MUTZ-3 were pre-incubated with the aCD40/aCD28-bispecific diabody, loaded with the heteroclitic variant of the aa988 epitope of hTERT, and used as stimulator cells in an HLA-A2-matched allogeneic in vitro CTL induction protocol. In total nine parallel bulk cultures, were stimulated twice with peptide-loaded MUTZ-3 DC, either pulsed with control protein or the aCD40/aCD28-bispecific diabody. hTERT988Y-specific CD8+ T cells could be detected in 5/9 individual cultures when stimulated with DC pulsed with the aCD40/aCD28-bispecific diabody, whereas in only 1/9 individual cultures hTERT988Y-specific CD8+ T cells could be detected when stimulated with DC pulsed with the control protein. Thus, priming efficacy of tumor-specific cytotoxic T cells can also be improved by cross-linking AML-DC and T cells with the αCD40/αCD28 diabody. We propose that the αCD40/αCD28-bispecific diabody can serve as a potent therapeutic tool to effectively augment anti-tumor T cell responses elicited by AML-DC.

scholarly journals Polysome arrest restricts miRNA turnover by preventing exosomal export of miRNA in growth-retarded mammalian cells

2015 ◽  
Vol 26 (6) ◽  
pp. 1072-1083 ◽  
Author(s):  
Souvik Ghosh ◽  
Mainak Bose ◽  
Anirban Ray ◽  
Suvendra N. Bhattacharyya
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Subcellular Distribution ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Mature Mirnas ◽  
Regulatory Rnas ◽  
The Stability ◽  
External Stimuli

MicroRNAs (miRNAs) are tiny posttranscriptional regulators of gene expression in metazoan cells, where activity and abundance of miRNAs are tightly controlled. Regulated turnover of these regulatory RNAs is important to optimize cellular response to external stimuli. We report that the stability of mature miRNAs increases inversely with cell proliferation, and the increased number of microribonucleoproteins (miRNPs) in growth-restricted mammalian cells are in turn associated with polysomes. This heightened association of miRNA with polysomes also elicits reduced degradation of target mRNAs and impaired extracellular export of miRNA via exosomes. Overall polysome sequestration contributes to an increase of cellular miRNA levels but without an increase in miRNA activity. Therefore miRNA activity and turnover can be controlled by subcellular distribution of miRNPs that may get differentially regulated as a function of cell growth in mammalian cells.

scholarly journals Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

2003 ◽  
Vol 2 (4) ◽  
pp. 778-787 ◽  
Author(s):  
Andrew Maselli ◽  
Ruth Furukawa ◽  
Susanne A. M. Thomson ◽  
Richard C. Davis ◽  
Marcus Fechheimer
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Cellular Response ◽  
Biological Function ◽  
Point Mutations ◽  
Actin Binding ◽  
Cross Linking ◽  
Hirano Bodies ◽  
Transmission Electron ◽  
Ef Hand

ABSTRACT Hirano bodies are paracrystalline actin filament-containing structures reported to be associated with a variety of neurodegenerative diseases. However, the biological function of Hirano bodies remains poorly understood, since nearly all prior studies of these structures were done with postmortem samples of tissue. In the present study, we generated a full-length form of a Dictyostelium 34-kDa actin cross-linking protein with point mutations in the first putative EF hand, termed 34-kDa ΔEF1. The 34-kDa ΔEF1 protein binds calcium normally but has activated actin binding that is unregulated by calcium. The expression of the 34-kDa ΔEF1 protein in Dictyostelium induces the formation of Hirano bodies, as assessed by both fluorescence microscopy and transmission electron microscopy. Dictyostelium cells bearing Hirano bodies grow normally, indicating that Hirano bodies are not associated with cell death and are not deleterious to cell growth. Moreover, the expression of the 34-kDa ΔEF1 protein rescues the phenotypes of cells lacking the 34-kDa protein and cells lacking both the 34-kDa protein and α-actinin. Finally, the expression of the 34-kDa ΔEF1 protein also initiates the formation of Hirano bodies in cultured mouse fibroblasts. These results show that the failure to regulate the activity and/or affinity of an actin cross-linking protein can provide a signal for the formation of Hirano bodies. More generally, the formation of Hirano bodies is a cellular response to or a consequence of aberrant function of the actin cytoskeleton.

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