scholarly journals Dynamics of fibril collagen remodeling by tumor cells using individual cell-based mathematical modeling

2021 ◽  
Author(s):  
Sharan Poonja ◽  
Mehdi Damaghi ◽  
Katarzyna A. Rejniak

AbstractMany solid tumors are characterized by dense extracellular matrix (ECM) composed of various ECM fibril proteins that provide structural support and biological context for the residing cells. The growing tumor cell colonies are capable of remodeling the ECM structure in tumor immediate vicinity to form specific microenvironmental niches. The changes in fibril patterns of the collagen (one of the ECM proteins) surrounding the tumor can be visualized experimentally using both histology and fluorescent imaging. In particular, three diverse tumor associated collagen signatures (TACS) were identified and related to tumor behavior, such as benign growth or invasion. Here we will use an off-lattice hybrid agent-based model (MultiCell-LF) to identify the rules of cell-ECM interactions that guide the development of various patterns of alignment of the ECM fibrils.

Science ◽  
2009 ◽  
Vol 326 (5957) ◽  
pp. 1216-1219 ◽  
Author(s):  
Richard O. Hynes

The extracellular matrix (ECM) and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases. The ECM has many effects beyond providing structural support. ECM proteins typically include multiple, independently folded domains whose sequences and arrangement are highly conserved. Some of these domains bind adhesion receptors such as integrins that mediate cell-matrix adhesion and also transduce signals into cells. However, ECM proteins also bind soluble growth factors and regulate their distribution, activation, and presentation to cells. As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM.


1999 ◽  
Vol 77 (11) ◽  
pp. 1843-1855 ◽  
Author(s):  
Pamela S Bromberg ◽  
Kathleen M Gough ◽  
Ian MC Dixon

Collagen type I and III deposition in the cardiac extracellular matrix contributes significantly to myocardial dysfunction. Diffuse and focal fibrosis is believed to accompany human congestive cardiomyopathy (CCM) associated with congestive heart failure (CHF). The left ventricle collagen remodeling that occurs in the hamster model of CCM is marked by left ventricle fibrosis, hypertrophy and dilation, proceeded by CHF post 150 days of age. The objectives of our study were to (i) evaluate changes in collagen deposition in the right (RV) and left (LV) ventricular tissue of cardiomyopathic (CMP) and control (CON) myocardium using FTIR ATR spectroscopy, (ii) classify the normal and diseased heart tissue using linear discriminant analysis (LDA) aided by a genetic algorithm (GA) selection of spectroscopically diagnostic regions in the mid-IR region, (iii) rationalize the spectroscopic differences between left/right ventricle tissue as well as CON/CMP tissue according to the pathophysiology documented for the UM-X7.1 strain of CMP hamsters. The presence of collagen in the tissue was confirmed spectroscopically by observation of the collagen IR fingerprint in the 1000-1800 cm-1 region. Difference spectroscopy was utilized to substantiate which tissue under comparison exhibited pronounced collagen content. Multivariate analysis (LDA) was carried out on user-selected spectral subregions and compared to class separation based on spectral subregions chosen nonsubjectively by a GA. Our study confirmed that the animals experienced LV collagen remodeling denoted by focal rather than diffuse fibrosis. In addition, RV collagen remodeling, denoted by decreased RV collagen content, appeared to accompany the increased LV collagen deposition found for the CMP animals.Key words: FTIR spectroscopy, collagen, cardiomyopathy, genetic algorithm, linear discriminant analysis.


2018 ◽  
Vol 19 (10) ◽  
pp. 2912 ◽  
Author(s):  
Girdhari Rijal ◽  
Jing Wang ◽  
Ilhan Yu ◽  
David Gang ◽  
Roland Chen ◽  
...  

Porcine mammary fatty tissues represent an abundant source of natural biomaterial for generation of breast-specific extracellular matrix (ECM). Here we report the extraction of total ECM proteins from pig breast fatty tissues, the fabrication of hydrogel and porous scaffolds from the extracted ECM proteins, the structural properties of the scaffolds (tissue matrix scaffold, TMS), and the applications of the hydrogel in human mammary epithelial cell spatial cultures for cell surface receptor expression, metabolomics characterization, acini formation, proliferation, migration between different scaffolding compartments, and in vivo tumor formation. This model system provides an additional option for studying human breast diseases such as breast cancer.


2020 ◽  
Vol 40 (02) ◽  
pp. 180-188 ◽  
Author(s):  
Christine E. Dolin ◽  
Gavin E. Arteel

AbstractChronic fatty liver disease is common worldwide. This disease is a spectrum of disease states, ranging from simple steatosis (fat accumulation) to inflammation, and eventually to fibrosis and cirrhosis if untreated. The fibrotic stage of chronic liver disease is primarily characterized by robust accumulation of extracellular matrix (ECM) proteins (collagens) that ultimately impairs the function of the organ. The role of the ECM in early stages of chronic liver disease is less well-understood, but recent research has demonstrated that several changes in the hepatic ECM in prefibrotic liver disease are not only present but may also contribute to disease progression. The purpose of this review is to summarize the established and proposed changes to the hepatic ECM that may contribute to inflammation during earlier stages of disease development, and to discuss potential mechanisms by which these changes may mediate the progression of the disease.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3041
Author(s):  
Ren Jie Tuieng ◽  
Sarah H. Cartmell ◽  
Cliona C. Kirwan ◽  
Michael J. Sherratt

Exposure to sub-lethal doses of ionising and non-ionising electromagnetic radiation can impact human health and well-being as a consequence of, for example, the side effects of radiotherapy (therapeutic X-ray exposure) and accelerated skin ageing (chronic exposure to ultraviolet radiation: UVR). Whilst attention has focused primarily on the interaction of electromagnetic radiation with cells and cellular components, radiation-induced damage to long-lived extracellular matrix (ECM) proteins has the potential to profoundly affect tissue structure, composition and function. This review focuses on the current understanding of the biological effects of ionising and non-ionising radiation on the ECM of breast stroma and skin dermis, respectively. Although there is some experimental evidence for radiation-induced damage to ECM proteins, compared with the well-characterised impact of radiation exposure on cell biology, the structural, functional, and ultimately clinical consequences of ECM irradiation remain poorly defined.


Author(s):  
Ubaid M. Al-Saggaf ◽  
Muhammad Usman ◽  
Imran Naseem ◽  
Muhammad Moinuddin ◽  
Ahmad A. Jiman ◽  
...  

Extracelluar matrix (ECM) proteins create complex networks of macromolecules which fill-in the extracellular spaces of living tissues. They provide structural support and play an important role in maintaining cellular functions. Identification of ECM proteins can play a vital role in studying various types of diseases. Conventional wet lab–based methods are reliable; however, they are expensive and time consuming and are, therefore, not scalable. In this research, we propose a sequence-based novel machine learning approach for the prediction of ECM proteins. In the proposed method, composition of k-spaced amino acid pair (CKSAAP) features are encoded into a classifiable latent space (LS) with the help of deep latent space encoding (LSE). A comprehensive ablation analysis is conducted for performance evaluation of the proposed method. Results are compared with other state-of-the-art methods on the benchmark dataset, and the proposed ECM-LSE approach has shown to comprehensively outperform the contemporary methods.


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