Extracellular Matrix Stiffness Modulates Microvascular Morphology During Early Sprouting Angiogenesis In Vitro

2009 ◽  
Author(s):  
Laxminarayanan Krishnan ◽  
Urs Utzinger ◽  
Steve Maas ◽  
Shawn Reese ◽  
Jeffrey A. Weiss ◽  
...  
Keyword(s):  
Matrix Stiffness ◽  
Matrix Rigidity ◽  
Cellular Functions ◽  
Sprouting Angiogenesis ◽  
Vascular Morphology ◽  
The Matrix ◽  
Extracellular Matrix Stiffness ◽  
Local Stiffness ◽  
Matrix Orientation

Sprouting angiogenesis is associated with changes in matrix stiffness[1]. Neovessel growth and morphology are in turn affected by the changes in matrix orientation or forces acting on the matrix[2]. Matrix rigidity influences the formation of cord like structures[3, 4] and could play a role in development of tissue specific vascular morphology or inhibit cellular functions in diseases. The effect of matrix stiffness on neovessel growth from preformed vasculature has not been examined. Matrix stiffness could be increased both by an increase in matrix density[5] as well as increased crosslink formation, as in hyperglycemia[6]. It is thus essential to first identify the effect of increase in local stiffness alone, in the absence of artificially induced crosslinks, which may interfere with matrix orientation. Our aim is to characterize changes in early angiogenesis associated with ECM of different densities and relate these to changes in matrix orientation.

Matrix stiffness-regulated cellular functions under different dimensionalities

2020 ◽  
Vol 8 (10) ◽  
pp. 2734-2755 ◽  
Author(s):  
Jiajun Zhong ◽  
Yuexiong Yang ◽  
Liqiong Liao ◽  
Chao Zhang
Keyword(s):  
Matrix Stiffness ◽  
Cellular Functions

The microenvironments that cells encounter with in vitro.

Mechanoregulation of cardiac myofibroblast differentiation: implications for cardiac fibrosis and therapy

2015 ◽  
Vol 309 (4) ◽  
pp. H532-H542 ◽  
Author(s):  
Kar Wey Yong ◽  
YuHui Li ◽  
GuoYou Huang ◽  
Tian Jian Lu ◽  
Wan Kamarul Zaman Wan Safwani ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Three Dimensional ◽  
Myofibroblast Differentiation ◽  
Matrix Stiffness ◽  
Extracellular Matrix Stiffness ◽  
Mechanical Microenvironment

Cardiac myofibroblast differentiation, as one of the most important cellular responses to heart injury, plays a critical role in cardiac remodeling and failure. While biochemical cues for this have been extensively investigated, the role of mechanical cues, e.g., extracellular matrix stiffness and mechanical strain, has also been found to mediate cardiac myofibroblast differentiation. Cardiac fibroblasts in vivo are typically subjected to a specific spatiotemporally changed mechanical microenvironment. When exposed to abnormal mechanical conditions (e.g., increased extracellular matrix stiffness or strain), cardiac fibroblasts can undergo myofibroblast differentiation. To date, the impact of mechanical cues on cardiac myofibroblast differentiation has been studied both in vitro and in vivo. Most of the related in vitro research into this has been mainly undertaken in two-dimensional cell culture systems, although a few three-dimensional studies that exist revealed an important role of dimensionality. However, despite remarkable advances, the comprehensive mechanisms for mechanoregulation of cardiac myofibroblast differentiation remain elusive. In this review, we introduce important parameters for evaluating cardiac myofibroblast differentiation and then discuss the development of both in vitro (two and three dimensional) and in vivo studies on mechanoregulation of cardiac myofibroblast differentiation. An understanding of the development of cardiac myofibroblast differentiation in response to changing mechanical microenvironment will underlie potential targets for future therapy of cardiac fibrosis and failure.

scholarly journals Soft limbal niche maintains stem cell compartmentalization and function through YAP

2021 ◽  
Author(s):  
Swarnabh Bhattacharya ◽  
Abhishek Mukherjee ◽  
Sabrina Pisano ◽  
Anna Altshuler ◽  
Waseem Nasser ◽  
...  
Keyword(s):  
Matrix Rigidity ◽  
Wound Healing Response ◽  
The Matrix ◽  
Niche Formation ◽  
Cell Compartmentalization ◽  
And Function ◽  
Extracellular Environment

Stem cells (SCs) decision to self-renew or differentiate largely depends on the extracellular environment and elasticity of their niche. A well-described mediator of the mechanotransduction pathway is the co-transcriptional activator Yes-associated protein (YAP), known to shuttle into the nucleus of cells grown on stiff matrices. YAP is also known to be essential for stemness, but confusingly, SCs often reside in soft niches. Furthermore, the role of matrix rigidity in niche formation and SC function in vivo is poorly understood. Here we report that the post-natal development of the murine corneal epithelium involves matrix stiffening and loss of YAP activity that is associated with the formation of differentiation compartment. Importantly, manipulating the matrix crosslinking enzyme, Lox, perturbed SC mark expression and resulted in loss of corneal transparency. In agreement, we found that YAP and mechanotransduction pathways are essential for stemness in the soft niche compartment, wound healing response, and dedifferentiation of committed cells into SCs following SC depletion. In vitro experiments revealed that stiffer substrates induced cytoplasmic YAP localization through activation of LATS1/2, facilitating SMAD2/3-mediated cell differentiation. Taken together, we propose that the soft environment of the corneal SC niche maintains YAP activity to support SC regulation during morphogenesis, adult homeostasis and regeneration by the niche.

Correlation Between Cellular Functions and Morphological Changes of Human Trophoblast in Vitro

1975 ◽  
Vol 33 ◽  
pp. 600-601
Author(s):  
John C. Garancis ◽  
Robert O. Hussa ◽  
Michael T. Story ◽  
Donald Yorde ◽  
Roland A. Pattillo
Keyword(s):  
Electron Microscopy ◽  
Cellular Proliferation ◽  
Morphological Changes ◽  
Culture Fluid ◽  
Cellular Functions ◽  
Human Trophoblast ◽  
Transmission Electron ◽  
Marked Activity ◽  
Malignant Trophoblast

Human malignant trophoblast cells in continuous culture were incubated for 3 days in medium containing 1 mM N6-O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) and 1 mM theophylline. The culture fluid was replenished daily. Stimulated cultures secreted many times more chorionic gonadotropin and estrogens than did control cultures in the absence of increased cellular proliferation. Scanning electron microscopy revealed remarkable surface changes of stimulated cells. Control cells (not stimulated) were smooth or provided with varying numbers of microvilli (Fig. 1). The latter, usually, were short and thin. The surface features of stimulated cells were considerably different. There was marked increase of microvilli which appeared elongated and thick. Many cells were covered with confluent polypoid projections (Fig. 2). Transmission electron microscopy demonstrated marked activity of cytoplasmic organelles. Mitochondria were increased in number and size; some giant forms with numerous cristae were observed.

Matrix stiffness modulates inhibition of HCV replication by Fluvastatin in vitro

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
J Kah ◽  
J Schrader ◽  
A Wüstenberg ◽  
G Tiegs ◽  
G Sass
Keyword(s):  
Matrix Stiffness

Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet
Keyword(s):  
Rabbit Aorta ◽  
Balloon Injury ◽  
Recombinant Hirudin ◽  
Aorta Wall ◽  
Thrombin Activity ◽  
Before And After ◽  
The Matrix

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

Formulation and Evaluation of Galantamine Hydrobromide Floating Matrix Tablet

2018 ◽  
Vol 8 (2) ◽  
Author(s):  
Poreddy Srikanth Reddy ◽  
Penjuri Subhash Chandra Bose ◽  
Vuppula Sruthi ◽  
Damineni Saritha
Keyword(s):  
Sodium Alginate ◽  
Xanthan Gum ◽  
Lag Time ◽  
Matrix Tablets ◽  
In Vitro Dissolution ◽  
Matrix Tablet ◽  
Compression Technique ◽  
Weight Variation ◽  
The Matrix

The aim of the present work was to prepare floating tablets of galantamine HBr using sodium alginate and xanthan gum as matrix forming carriers. Galantamine HBr is used for the treatment of mild to moderate Alzheimer's disease and various other memory impairments, in particular those of vascular origin. The matrix tablet formulations were prepared by varying the concentrations of sodium alginate and xanthan gum. The tablets were prepared by direct compression technique using PVP K-30 as a binder and sodium bicarbonate for development of CO2. The prepared matrix tablets were evaluated for properties such as hardness, thickness, friability, weight variation, floating lag time, compatibility using DSC and FTIR. In vitro dissolution was carried out for 12 hrs in 0.1N HCl at 37±0.5 ºC using USP paddle type dissolution apparatus. It was noted that, all the prepared formulations had desired floating lag time and constantly floated on dissolution medium by maintaining the matrix integrity. The drug release from prepared tablets was found to vary with varying concentration of the polymers, sodium alginate and xanthan gum. From the study it was concluded that floating drug delivery system for galantamine HBr can be prepared by using sodium alginate and xanthan gum as a carrier.

Investigation of the effect of loratadine and calcium ions on oxidoreductase activity of catalase enzyme

2020 ◽  
Vol 16 ◽  
Author(s):  
Edhem Hasković ◽  
Safija Herenda ◽  
Zehra Halilović ◽  
Snežana Unčanin ◽  
Denis Hasković ◽  
...  
Keyword(s):  
Calcium Ions ◽  
Enzyme Reaction ◽  
Analytical Techniques ◽  
Competitive Inhibitor ◽  
Cellular Functions ◽  
Oxidoreductase Activity ◽  
H1 Antihistamines ◽  
Activity Of Enzymes ◽  
The Given

Background: The Spectrophotometric method is one of the most suitable analytical techniques for testing the activity of enzymes under the influence of various factors. Methods: The effect of H1-antihistamines of loratadine and calcium ions on enzyme catalase under in vitro conditions was investigated in this paper. Results and Discussion: It has been shown that loratadine isa partial inhibitor of catalase, but this effect is diminished in the presence of calcium ions. Calcium as well as other cations are important for many biological and cellular functions. The kidneys play a central role in the homeostasis of these ions. The activity of the catalase enzyme under the given conditions, the type of inhibition,and the kinetic parameters of the enzyme reaction were determined. Conclusion: We concluded that loratadine is a partially competitive inhibitor.

scholarly journals Internalization of Foldamer-Based DNA Mimics through a Site-Specific Antibody Conjugate to Target HER2-Positive Cancer Cells

2021 ◽  
Vol 14 (7) ◽  
pp. 624
Author(s):  
Valentina Corvaglia ◽  
Imène Ait Mohamed Amar ◽  
Véronique Garambois ◽  
Stéphanie Letast ◽  
Aurélie Garcin ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Topoisomerase I ◽  
Ovarian Cancer Cells ◽  
Cellular Functions ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Dna Topoisomerase ◽  
Antibody Conjugate ◽  
A Site

Inhibition of protein–DNA interactions represents an attractive strategy to modulate essential cellular functions. We reported the synthesis of unique oligoamide-based foldamers that adopt single helical conformations and mimic the negatively charged phosphate moieties of B-DNA. These mimics alter the activity of DNA interacting enzymes used as targets for cancer treatment, such as DNA topoisomerase I, and they are cytotoxic only in the presence of a transfection agent. The aim of our study was to improve internalization and selective delivery of these highly charged molecules to cancer cells. For this purpose, we synthesized an antibody-drug conjugate (ADC) using a DNA mimic as a payload to specifically target cancer cells overexpressing HER2. We report the bioconjugation of a 16-mer DNA mimic with trastuzumab and its functional validation in breast and ovarian cancer cells expressing various levels of HER2. Binding of the ADC to HER2 increased with the expression of the receptor. The ADC was internalized into cells and was more efficient than trastuzumab at inhibiting their growth in vitro. These results provide proof of concept that it is possible to site-specifically graft high molecular weight payloads such as DNA mimics onto monoclonal antibodies to improve their selective internalization and delivery in cancer cells.

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