Matrix Modulus Affects Invasion Rate of Tumor Cells through Synthetic Hydrogels

2012 ◽  
Vol 1418 ◽  
Author(s):  
Esmaiel Jabbari

ABSTRACTUnderstanding factors affecting cell invasion influences the design of engineered constructs for tissue regeneration. The objective of this work was to investigate the effect of matrix stiffness on invasion of tumor cells through a synthetic hydrogel with well-defined properties. A novel star acrylate-functionalized polyethylene glycol-co-lactide (SPELA) macromer was synthesized to produce hydrogels with well-defined water content, elastic modulus, degree of crosslinking and hydrophilicity. The hydrogel was formed by photo-polymerization of the macromer with or without integrin-binding cell adhesive RGD peptide. Cell invasion experiments were carried out in a transwell with SPELA hydrogel as the invading matrix and 4T1 mouse breast cancer cells. The invading cells on the lower membrane side were counted with an inverted fluorescent microscope. The concentration of SPELA macromer ranged from 10-25 wt% and that of RGD ranged from 1x10-4 to 1x10-2 M. The shear modulus of the hydrogel varied from 200 Pa to 25 kPa as the SPELA concentration increased from 10 to 25 wt%. Cell invasion slightly increased with increasing RGD concentration. However, RGD concentration >1% resulted in a significant decrease in cell migration. As the matrix stiffness increased from 0.15 to 0.4, 3, 5, 6, 14, and 25 kPa the invasion rate decreased from 18.0 to 5.5, 6, 5.7, 5.2, 1.5, and 1.0 cells/mm2/h, respectively. There was a sharp decrease in invasion rate for matrix stiffness greater than 10 kPa. Results demonstrate that matrix stiffness plays a major role in invasion of tumor cell through a gelatinous matrix.

2010 ◽  
Vol 55 (4) ◽  
Author(s):  
Adriana Aguado-Martínez ◽  
Gema Álvarez-García ◽  
Gereon Schares ◽  
Verónica Risco-Castillo ◽  
Aurora Fernández-García ◽  
...  

AbstractNeospora caninum negatively impacts bovine reproductive performance around the world. Addressing this problem requires a greater understanding of the parasite’s molecular biology. In this study, monoclonal antibodies against recombinant proteins were successfully developed and employed to characterise two different proteins of N. caninum: the acute phase-associated NcGRA7 and the chronic phase-associated NcSAG4. Immunofluorescence with the anti-rNcGRA7 monoclonal antibody suggested that NcGRA7 trafficks from tachyzoite dense granules to the matrix of the parasitophorous vacuole and parasite’s surroundings. Furthermore, NcGRA7 is also expressed in the bradyzoite stage and localised on the matrix of bradyzoite-positive vacuoles. NcGRA7 appears to be partially involved in the tachyzoite-invasion mechanisms, as an anti-rNcGRA7 monoclonal antibody partially inhibited in vitro tachyzoite-invasion. A monoclonal antibody specific for NcSAG4 confirmed this protein’s bradyzoitespecific expression both by western blot and immunofluorescence. However, some bradyzoite-positive vacuoles only weakly expressed NcSAG4, if it was expressed at all. The specificity of the anti-rNcSAG4 monoclonal antibody was confirmed by the recognition of the NcSAG4 in the membrane surface of Nc-1SAG4c transgenic tachyzoites, which constitutively expresses NcSAG4. Blocking NcSAG4 of Nc-1SAG4c tachyzoites with the monoclonal antibody did not affect host cell invasion. However, its implication on the host cell adhesion or host immune evasion should not be discarded.


2013 ◽  
Vol 104 (2) ◽  
pp. 148a
Author(s):  
Maryam Riaz ◽  
Marie Versaevel ◽  
Sylvain Gabriele
Keyword(s):  

2017 ◽  
Vol 28 (22) ◽  
pp. 2958-2977 ◽  
Author(s):  
Y. A. Miroshnikova ◽  
G. I. Rozenberg ◽  
L. Cassereau ◽  
M. Pickup ◽  
J. K. Mouw ◽  
...  

Tumors are fibrotic and characterized by abundant, remodeled, and cross-linked collagen that stiffens the extracellular matrix stroma. The stiffened collagenous stroma fosters malignant transformation of the tissue by increasing tumor cell tension to promote focal adhesion formation and potentiate growth factor receptor signaling through kinase. Importantly, collagen cross-linking requires fibronectin (FN). Fibrotic tumors contain abundant FN, and tumor cells frequently up-regulate the FN receptor α5β1 integrin. Using transgenic and xenograft models and tunable two- and three-dimensional substrates, we show that FN-bound α5β1 integrin promotes tension-dependent malignant transformation through engagement of the synergy site that enhances integrin adhesion force. We determined that ligation of the synergy site of FN permits tumor cells to engage a zyxin-stabilized, vinculin-linked scaffold that facilitates nucleation of phosphatidylinositol (3,4,5)-triphosphate at the plasma membrane to enhance phosphoinositide 3-kinase (PI3K)-dependent tumor cell invasion. The data explain why rigid collagen fibrils potentiate PI3K activation to promote malignancy and offer a perspective regarding the consistent up-regulation of α5β1 integrin and FN in many tumors and their correlation with cancer aggression.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Demin Chen ◽  
Wei Long ◽  
Yanyan Li ◽  
Rui Zhang

The gas loss in sampling is the root of coalbed gas content measurement error. The pressure and particle size have a significant impact on the gas loss. Using the self-developed coal particle pneumatic pipeline transportation experimental system, this study investigated the pressure and particle size changes in the sampling pipeline. It is found that the sampling process can be divided into four stages: no flow field stage, sample outburst stage, stable conveying stage, and tail purging stage. The extreme pressure in the sampling pipeline appears at the sample outburst stage; and the pressure in the pipeline has levelled off after sharp decrease in the stable conveying stage. It is also found that the extreme pressure increases first and then decreases with the increase of particle size. The duration of outburst stage is negatively correlated with particle size, and that of stable conveying stage is positively correlated with particle size. In addition, the results show that the loss rate of 1–3 mm particles is the smallest after the test but that particles less than 1 mm increase by about two times and particles greater than 3 mm decrease by more than three times. The study also shows that the particle size distribution of coal samples is a single peak with left skew distribution, and the gas reverse circulation sampling test does not change the location of the peak but makes it higher and sharper. The single size coal sample is more likely to collide than the mixture. This study can help to advance the understanding of impact factors on gas loss during reverse circulation sampling.


2011 ◽  
Vol 4 (2) ◽  
pp. 153-183 ◽  
Author(s):  
Diana Carter ◽  
Peredur Davies ◽  
Margaret Deuchar ◽  
María del Carmen Parafita Couto

AbstractIn this paper we compare the code-switching (CS) patterns in three bilingual corpora collected in Wales, Miami and Patagonia, Argentina. Using the Matrix Language Framework to do a clause-based analysis of a sample of data, we consider the impact of structural relationships and extra-linguistic factors on CS patterns. We find that the Matrix Language (ML) is uniform where the language pairs have contrasting word orders, as in Welsh-English (VSO-SVO) and WelshSpanish (VSO-SVO) but diverse where the word order is similar as in Spanish-English (SVO-SVO). We find that the diversity of the ML in Miami is related to the diversity of degrees of proficiency, ethnic identities, and social networks amongst members of that community, while the uniformity of the ML in Wales is related to the uniformity of these factors. This is not so clear in Patagonia, however, where there is little CS produced in conversation. We suggest that the members of the speech community use Spanish or Welsh mostly in a monolingual mode, depending on the interlocutor and the social situation.


Oncotarget ◽  
2018 ◽  
Vol 9 (53) ◽  
pp. 30034-30052 ◽  
Author(s):  
Michelle M. Noonan ◽  
Magdalena Dragan ◽  
Michael M. Mehta ◽  
David A. Hess ◽  
Muriel Brackstone ◽  
...  

2017 ◽  
Vol 16 (01) ◽  
pp. 1650023
Author(s):  
Alexandra M. Brown ◽  
Yoliem S. Miranda-Alarćon ◽  
Grant A. Knoll ◽  
Anthony M. Santora ◽  
Ipsita A. Banerjee

In this work, self-assembled tumor targeting nanostructured surfaces were developed from a newly designed amphiphile by conjugating boc protected isoleucine with 2,[Formula: see text] ethylenedioxy bis ethylamine (IED). To target mouse mammary tumor cells, a short peptide sequence derived from the human alpha-fetoprotein (AFP), LSEDKLLACGEG was attached to the self-assembled nanostructures. Tumor targeting and cell proliferation were examined in the presence of nanoscale assemblies. To further obliterate mouse breast tumor cells, the chemotherapeutic drug tamoxifen was then entrapped into the nanoassemblies. Our studies indicated that the targeting systems were able to efficiently encapsulate and release tamoxifen. Cell proliferation studies showed that IED-AFP peptide loaded with tamoxifen decreased the proliferation of breast cancer cells while in the presence of the IED-AFP peptide nanoassemblies alone, the growth was relatively slower. In the presence of human dermal fibroblasts however cell proliferation continued similar to controls. Furthermore, the nanoscale assemblies were found to induce apoptosis in mouse breast cancer cells. To examine live binding interactions, SPR analysis revealed that tamoxifen encapsulated IED-AFP peptide nanoassemblies bound to the breast cancer cells more efficiently compared to unencapsulated assemblies. Thus, we have developed nanoscale assemblies that can specifically bind to and target tumor cells, with increased toxicity in the presence of a chemotherapeutic drug.


1985 ◽  
Vol 100 (5) ◽  
pp. 1369-1378 ◽  
Author(s):  
J R Apgar ◽  
S H Herrmann ◽  
J M Robinson ◽  
M F Mescher

It has been shown that a Triton X-100-insoluble protein matrix can be isolated from the plasma membranes of P815 tumor cells and murine lymphoid cells (Mescher, M. F., M. J. L. Jose and S. P. Balk, 1981, Nature (Lond.), 289:139-144). The properties of the matrix suggested that this set of proteins might form a membrane skeletal structure, stable in the absence of the lipid bilayer. Since purification of plasma membrane results in yields of only 20 to 40%, it was not clear whether the matrix was associated with the entire plasma membrane. To determine if a detergent-insoluble structure was present over the entire cell periphery and stable in the absence of the membrane bilayer or cytoskeletal components, we have examined extraction of whole cells with Triton X-100. Using the same conditions as those used for isolation of the matrix from membranes, we found that extraction of intact cells resulted in structures consisting of a continuous layer of protein at the periphery, a largely empty cytoplasmic space, and a nuclear remnant. Little or no lipid bilayer structure was evident in association with the peripheral layer, and no filamentous cytoskeletal structures could be seen in the cytoplasmic space by thin-section electron microscopy. Analysis of these Triton shells showed them to retain approximately 15% of the total cell protein, most of which was accounted for by low molecular weight nuclear proteins. 5'-Nucleotidase, a cell surface enzyme that remains associated with the plasma membrane matrix, was quantitatively recovered with the shells. Included among the polypeptides present in the shells was a set with mobilities identical to those of the set that makes up the plasma membrane matrix. The polypeptide composition of the shells further confirmed that cytoskeletal proteins were present to a very low extent, if at all, after the extraction. The results demonstrate that a detergent-insoluble protein matrix associated with the periphery of these cells forms a continuous, intact macrostructure whose stability is independent of the membrane bilayer or filamentous cytoskeletal elements, and thus has the properties of a membrane skeletal structure. Although not yet directly demonstrated, the results also strongly suggest that this peripheral layer is composed of the previously described set of plasma membrane matrix proteins. This article discusses possible roles for this proposed membrane skeletal structure in stabilizing the membrane bilayer and affecting the dynamics of other membrane proteins.


2016 ◽  
Vol 701 ◽  
pp. 225-229 ◽  
Author(s):  
Sivanesan Sivakumar ◽  
Hsien Loong Teow ◽  
Ramesh Singh ◽  
Ali Niakan ◽  
Nobuyuki Mase

A small amount of iron oxide (Fe2O3) was added to the commercially available 3 mol% Y-TZP as a sintering aid over a temperature range of 1250°C to 1500°C. Sintered samples were then evaluated to determine the bulk density, Vickers hardness, and fracture toughness. In addition, hydrothermal ageing experiments to determine the tetragonal phase stability were performed on selected sintered samples in superheated steam at 180°C / 10 bar for up to 24 hours. Based on the work carried out, it was revealed that additions of Fe2O3 particularly 0.3 wt% was indeed beneficial in aiding densification, improving the matrix stiffness and hardness when compared to undoped Y-TZP sintered at temperatures below 1350°C. Addition of Fe2O3 was found to have negligible effects on the fracture toughness of all samples with the exception of the 0.5 and 1 wt% doped Y-YZP sintered above 1400°C. Hydrothermal ageing resistance of Y-TZP was found to be enhanced with the addition of Fe2O3 in the Y-TZP matrix.


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