scholarly journals A finite dissipative theory of temporary interfibrillar bridges in the extracellular matrix of ligaments and tendons

2008 ◽  
Vol 6 (39) ◽  
pp. 909-924 ◽  
Author(s):  
P. Ciarletta ◽  
M. Ben Amar

The structural integrity and the biomechanical characteristics of ligaments and tendons result from the interactions between collagenous and non-collagenous proteins (e.g. proteoglycans, PGs) in the extracellular matrix. In this paper, a dissipative theory of temporary interfibrillar bridges in the anisotropic network of collagen type I, embedded in a ground substance, is derived. The glycosaminoglycan chains of decorin are assumed to mediate interactions between fibrils, behaving as viscous structures that transmit deformations outside the collagen molecules. This approach takes into account the dissipative effects of the unfolding preceding fibrillar elongation, together with the slippage of entire fibrils and the strain-rate-dependent damage evolution of the interfibrillar bridges. Thermodynamic consistency is used to derive the constitutive equations, and the transition state theory is applied to model the rearranging properties of the interfibrillar bridges. The constitutive theory is applied to reproduce the hysteretic spectrum of the tissues, demonstrating how PGs determine damage evolution, softening and non-recoverable strains in their cyclic mechanical response. The theoretical predictions are compared with the experimental response of ligaments and tendons from referenced studies. The relevance of the proposed model in mechanobiology research is discussed, together with several applications from medical practice to bioengineering science.

2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 35-35
Author(s):  
Maegan A Reeves ◽  
Courtney E Charlton ◽  
Terry D Brandebourg

Abstract Given adipose tissue is histologically classified as connective tissue, we hypothesized expression of extracellular matrix (ECM) components are significantly altered during adipogenesis. However, little is known about the regulation of the ECM during adipose tissue development in the pig. Therefore, the objective of this study was to characterize expression of ECM components during porcine adipogenesis. Primary cultures of adipose tissue stromal-vascular cells were harvested from 3-day-old neonatal pigs (n=6) and preadipocytes induced to differentiate in vitro for 8 days in the presence of insulin, hydrocortisone, and rosiglitazone. Total RNA was extracted from these cultures on days 0 and 8 post-induction. Real-time PCR was then utilized to determine changes in mRNA expression for collagen type I alpha 1 chain (COL1A), collagen type I alpha 2 chain (COL2A), collagen type I alpha 3 chain (COL3A), collagen type I alpha 4 chain (COL4A), collagen type I alpha 6 chain (COL6A), biglycan, fibronectin, laminin, nitogen-1 (NID1), matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9), metallopeptidase inhibitor 3 (TIMP3). The mRNA abundances of COL1A, COL3A and MMP2 were significantly downregulated 2.86-fold (P < 0.05), 16.7-fold (P < 0.01) and 3.1-fold (P < 0.05) respectively in day 8 (differentiated) compared to day 0 (undifferentiated) cultures. Meanwhile, mRNA abundances were significantly upregulated during adipogenesis for the COL2A (2.82-fold; P < 0.05), COL4A (2.01-fold; P < 0.05), COL6A (2.8-fold; P < 0.05), biglycan (49.9- fold; P < 0.001), fibronectin (452-fold; P < 0.001), laminin (6.1-fold; P < 0.05), NID1(47.4-fold; P < 0.01), MMP9 (76.8- fold; P < 0.01), and TIMP3(3.04-fold; P < 0.05) genes. These data support the hypothesis that significant changes in ECM components occur during porcine adipogenesis. Modulating adipose tissue ECM remodeling might be a novel strategy to manipulate adiposity in the pig.


2016 ◽  
Vol 11 ◽  
pp. BMI.S38439 ◽  
Author(s):  
Federica Genovese ◽  
Zsolt S. Kàrpàti ◽  
Signe H. Nielsen ◽  
Morten A. Karsdal

The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) surgery of the right ureter. The left kidney (contralateral) was used as internal control. Six rats were sham operated and used as the control group. Rats were terminated two weeks after the surgery; the kidneys were excised and precision-cut kidney slices (PCKSs) were cultured for five days in serum-free medium. Markers of collagen type I formation (P1NP), collagen type I and III degradation (C1M and C3M), and α-smooth muscle actin (αSMA) were measured in the PCKS supernatants by enzyme-linked immunosorbent assay. P1NP, C1M, C3M, and α-SMA were increased up to 2- to 13-fold in supernatants of tissue slices from the UUO-ligated kidneys compared with the contralateral kidneys ( P < 0.001) and with the kidneys of sham-operated animals ( P < 0.0001). The markers could also reflect the level of fibrosis in different animals. The UUO PCKS ex vivo model provides a valuable translational tool for investigating the extracellular matrix remodeling associated with renal interstitial fibrosis.


2011 ◽  
Vol 300 (4) ◽  
pp. C907-C918 ◽  
Author(s):  
Matilde Alique ◽  
Laura Calleros ◽  
Alicia Luengo ◽  
Mercedes Griera ◽  
Miguel Ángel Iñiguez ◽  
...  

Glomerular diseases are characterized by a sustained synthesis and accumulation of abnormal extracellular matrix proteins, such as collagen type I. The extracellular matrix transmits information to cells through interactions with membrane components, which directly activate many intracellular signaling events. Moreover, accumulating evidence suggests that eicosanoids derived from cyclooxygenase (COX)-2 participate in a number of pathological processes in immune-mediated renal diseases, and it is known that protein kinase B (AKT) may act through different transcription factors in the regulation of the COX-2 promoter. The present results show that progressive accumulation of collagen I in the extracellular medium induces a significant increase of COX-2 expression in human mesangial cells, resulting in an enhancement in PGE2 production. COX-2 overexpression is due to increased COX-2 mRNA levels. The study of the mechanism implicated in COX-2 upregulation by collagen I showed focal adhesion kinase (FAK) activation. Furthermore, we observed that the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway by collagen I and collagen I-induced COX-2 overexpression was abolished by PI3K and AKT inhibitors. Additionally, we showed that the cAMP response element (CRE) transcription factor is implicated. Finally, we studied COX-2 expression in an animal model, NG-nitro-l-arginine methyl ester hypertensive rats. In renal tissue and vascular walls, COX-2 and collagen type I content were upregulated. In summary, our results provide evidence that collagen type I increases COX-2 expression via the FAK/PI3K/AKT/cAMP response element binding protein signaling pathway.


2020 ◽  
Author(s):  
A. E. Hafner ◽  
N. G. Gyori ◽  
C. A. Bench ◽  
L. K. Davis ◽  
A. Šarić

One of the most robust examples of self-assembly in living organisms is the formation of collagen architectures. Collagen type I molecules are a crucial component of the extracellular-matrix where they self-assemble into fibrils of well defined striped patterns. This striped fibrilar pattern is preserved across the animal kingdom and is important for the determination of cell phenotype, cell adhesion, and tissue regulation and signalling. The understanding of the physical processes that determine such a robust morphology of self-assembled collagen fibrils is currently almost completely missing. Here we develop a minimal coarse-grained computational model to identify the physical principles of the assembly of collagen-mimetic molecules. We find that screened electrostatic interactions can drive the formation of collagen-like filaments of well-defined striped morphologies. The fibril pattern is determined solely by the distribution of charges on the molecule and is robust to the changes in protein concentration, monomer rigidity, and environmental conditions. We show that the fibril pattern cannot be easily predicted from the interactions between two monomers, but is an emergent result of multi-body interactions. Our results can help address collagen remodelling in diseases and ageing, and guide the design of collagen scaffolds for biotechnological applications.Statement of SignificanceCollagen type I protein is the most abundant protein in mammals. It is a crucial component of the extracellular-matrix where it robustly self-assembles into fibrils of specific striped architectures that are crucial for the correct collagen function. The molecular features that determine such robust fibril architectures are currently not well understood. Here we develop a minimal coarse-grained model to connect the design of collagen-like molecules to the architecture of the resulting self-assembled fibrils. We find that the pattern of charged residues on the surface of molecules can drive the formation of collagen-like fibrils and fully control their architectures. Our findings can help understand changes in collagen architectures observed in diseases and guide the design of synthetic collagen scaffolds.


2021 ◽  
Vol 73 (1) ◽  
pp. 103-110
Author(s):  
Braca Kundalic ◽  
Sladjana Ugrenovic ◽  
Ivan Jovanovic ◽  
Vladimir Petrovic ◽  
Aleksandar Petrovic ◽  
...  

The aim of this study was to analyze the expression of extracellular matrix (ECM) proteins in human endoneurium during aging. We harvested 15 cadaveric sural nerves, distributed in 3 age groups (I: 25-44, II: 45-64, III: 65-86 years old). Histological sections were stained immunohistochemically for the presence of collagen type I, type IV and laminin, and the ImageJ processing program was used in morphometrical analysis to determine the percentages of these endoneurial proteins. In two younger groups, the endoneurial matrix of the sural nerve was composed from about equal proportions of these proteins, which may be considered a favorable microenvironment for the regeneration of nerve fibers. Linear regression analysis showed a significant increase in endoneurial collagen type IV with age, while collagen type I and laminin significantly decreased during the aging process. In cases older than 65 years, remodeling of the endoneurial matrix was observed to be significantly higher for the presence of collagen type IV, and lower for the expression of collagen type I and laminin. This age-related imbalance of ECM proteins could represent a disadvantageous microenvironment for nerve fiber regeneration in older adults. Our findings contribute to the development of therapeutic approaches for peripheral nerve regeneration.


2020 ◽  
Vol 209 (2–3) ◽  
pp. 101-109
Author(s):  
Thai Thanh Hoang Thi ◽  
Diem Huong Tran Nguyen ◽  
Dinh Tien Dung  Nguyen ◽  
Dai Hai Nguyen ◽  
Minh-Dung Truong

The aim of this study was to develop a porcine epiphyseal plate-derived extracellular matrix powder (PEPEP) for epiphyseal plate regeneration. PEPEP was characterized by chemical assay to determine the contents of DNA and epiphyseal plate complex chemical components (glycosaminoglycan and hydroxyproline). The effects of PEPEP on the viability, proliferation, and differentiation of human bone marrow mesenchymal stem cells (hBMSCs) were also evaluated. hBMSCs cultured in PEPEP exhibited a good distribution with excellent viability after 72 h, demonstrating the ability of PEPEP to support hBMSC proliferation. At week 4 and 6 in vitro, the PEPEP + hBMSCs structure showed chondrogenic ability and an increase in expression of collagen type I, type II, and type X. PEPEP showed a promising ability to enhance cartilage formation and promote chondrocyte differentiation, maturation, and hypertrophy. The results provide insights into the feasibility of PEPEP as a potential material for tissue engineering applications.


2017 ◽  
Vol 27 (10) ◽  
pp. 1589-1600 ◽  
Author(s):  
Chenxu Cao ◽  
Zhiwu Zhu ◽  
Tiantian Fu ◽  
Zhijie Liu

The deformation of frozen soil under impact loading is usually accompanied by the evolution of internal defects and microdamage. By taking the strain and strain rates into account, a rate-dependent damage evolution law is proposed in this study, under the assumption of equivalent strain. Subsequently, a damage-modified rate-dependent constitutive model is proposed to describe the dynamic mechanical properties of frozen soil. A split Hopkinson pressure bar is utilized to test the dynamic mechanical response of frozen soil at different temperatures and high strain rates. The experimental results show that frozen soil produces obvious strain rate and temperature effects, and that there is a linear relationship between the peak stress and temperature. The theoretical results of the proposed constitutive model agree well with the experimental results, verifying the applicability of the model.


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