Collagen-Agarose Co-Gels as a Model for Collagen-Matrix Interaction in Soft Tissue

2011 ◽  
Author(s):  
Spencer P. Lake ◽  
Sadie Doggett ◽  
Victor H. Barocas
Keyword(s):  
Collagen Fiber ◽  
Type I Collagen ◽  
Soft Tissues ◽  
Experimental System ◽  
Model System ◽  
Type I ◽  
Collagen Gels ◽  
Fiber Network ◽  
Fibrillar Material

Connective soft tissues have complex mechanical properties that are determined by their collagen fiber network and surrounding non-fibrillar material. The mechanical role of non-fibrillar material and the nature of its interaction with the collagen network remain poorly understood, in part because of the lack of a simple experimental model system to examine and quantify these properties. The development of a simple but representational experimental system will allow for greater insight into the interaction between fibers and the non-fibrillar matrix. Reconstituted Type I collagen gels are an attractive model tissue for exploring micro- and macroscale relationships between constituents (e.g., [1–2]), but standard collagen gels lack the non-fibrillar components (i.e., proteoglycan, minor collagens, etc.) present in native tissue. A recent study [3] added low quantities of agarose to collagen gels, which dramatically increased the shear storage modulus with minimal changes to the collagen fiber network. In this study, we suggest that collagen-agarose co-gels can serve as a model system to investigate the mechanical role of non-fibrillar ECM. Even though agarose is relatively compliant at low concentrations, and collagen fibers are very stiff in tension, we hypothesized that the presence of agarose in co-gels would have a pronounced effect on structural response and mechanical behavior in tensile loading. Therefore, the objective of this study was to examine the properties of collagen-agarose co-gels to understand better the nature of, and the relationships between, the collagen fiber network and non-fibrillar matrix of simplified tissue analogs.

scholarly journals Micromechanics of cellularized biopolymer networks

2015 ◽  
Vol 112 (37) ◽  
pp. E5117-E5122 ◽  
Author(s):  
Christopher A. R. Jones ◽  
Matthew Cibula ◽  
Jingchen Feng ◽  
Emma A. Krnacik ◽  
David H. McIntyre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Optical Tweezers ◽  
Collagen Fiber ◽  
Type I Collagen ◽  
Qualitative Difference ◽  
Type I ◽  
Dependent Manner ◽  
Adhesion Forces ◽  
Collagen Gels ◽  
Fiber Network

Collagen gels are widely used in experiments on cell mechanics because they mimic the extracellular matrix in physiological conditions. Collagen gels are often characterized by their bulk rheology; however, variations in the collagen fiber microstructure and cell adhesion forces cause the mechanical properties to be inhomogeneous at the cellular scale. We study the mechanics of type I collagen on the scale of tens to hundreds of microns by using holographic optical tweezers to apply pN forces to microparticles embedded in the collagen fiber network. We find that in response to optical forces, particle displacements are inhomogeneous, anisotropic, and asymmetric. Gels prepared at 21 °C and 37 °C show qualitative difference in their micromechanical characteristics. We also demonstrate that contracting cells remodel the micromechanics of their surrounding extracellular matrix in a strain- and distance-dependent manner. To further understand the micromechanics of cellularized extracellular matrix, we have constructed a computational model which reproduces the main experiment findings.

Tissue inhibitor of metalloproteinases (TIMP) regulates extracellular type I collagen degradation by chondrocytes and endothelial cells

1987 ◽  
Vol 87 (2) ◽  
pp. 357-362
Author(s):  
J. Gavrilovic ◽  
R.M. Hembry ◽  
J.J. Reynolds ◽  
G. Murphy
Keyword(s):  
Endothelial Cells ◽  
Type I Collagen ◽  
Model System ◽  
Collagen Degradation ◽  
Type I ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Regulatory Factor ◽  
Tissue Inhibitor ◽  
Cells Cultured

A specific antiserum to purified rabbit tissue inhibitor of metalloproteinases (TIMP) was raised in sheep, characterized and used to investigate the role of TIMP in a model system. Chondrocytes and endothelial cells cultured on 14C-labelled type I collagen films and stimulated to produce collagenase were unable to degrade the films unless the anti-TIMP antibody was added. The degradation induced was inhibited by a specific anti-rabbit collagenase antibody. It was concluded that TIMP is a major regulatory factor in cell-mediated collagen degradation.

scholarly journals Multiscale Model Predicts Tissue-Level Failure From Collagen Fiber-Level Damage

2012 ◽  
Vol 134 (9) ◽  
Author(s):  
Mohammad F. Hadi ◽  
Edward A. Sander ◽  
Victor H. Barocas
Keyword(s):  
Type I Collagen ◽  
Soft Tissues ◽  
Mechanical Response ◽  
Collagen Gel ◽  
Multiscale Model ◽  
Tissue Level ◽  
Type I ◽  
Collagen Gels ◽  
Damage And Failure ◽  
Failure Data

Excessive tissue-level forces communicated to the microstructure and extracellular matrix of soft tissues can lead to damage and failure through poorly understood physical processes that are multiscale in nature. In this work, we propose a multiscale mechanical model for the failure of collagenous soft tissues that incorporates spatial heterogeneity in the microstructure and links the failure of discrete collagen fibers to the material response of the tissue. The model, which is based on experimental failure data derived from different collagen gel geometries, was able to predict the mechanical response and failure of type I collagen gels, and it demonstrated that a fiber-based rule (at the micrometer scale) for discrete failure can strongly shape the macroscale failure response of the gel (at the millimeter scale). The model may be a useful tool in predicting the macroscale failure conditions for soft tissues and engineered tissue analogs. In addition, the multiscale model provides a framework for the study of failure in complex fiber-based mechanical systems in general.

Initial Collagen Fiber Alignment Determines the Mechanical and Structural Response of Cell-Compacted Tissue-Equivalents Under Indentation

2011 ◽  
Author(s):  
Spencer P. Lake ◽  
Victor H. Barocas
Keyword(s):  
Collagen Fiber ◽  
Soft Tissues ◽  
Model System ◽  
Type I ◽  
Collagen Network ◽  
Fiber Alignment ◽  
Collagen Organization ◽  
Tissue Equivalents ◽  
Collagen Fiber Alignment ◽  
Indentation Site

The mechanical behavior of connective soft tissues depends largely on their structural organization, particularly of the collagen network. Previous studies have utilized polarized light imaging techniques to quantify collagen organization and fiber kinematics under tensile load (e.g., [1–2]). Many native tissues function in non-tensile loading environments, however, and the microstructural response to such loads is poorly understood. For example, fiber-reinforced soft tissues can be subjected to indentation in vivo (e.g., supraspinatus tendon in shoulder, flexor tendons that wrap around bones), resulting in a complex combination of compressive (near indentation site) and tensile forces (away from indentation site) being applied to the tissue. In order to understand and predict a tissue’s response to such loading, the respective roles of the collagen and non-fibrillar matrix must be elucidated. In particular, how do the properties of the collagen network (e.g., density/organization) and non-fibrillar matrix (e.g., type/quantity) modulate behavior under load? In order to address these questions, our group has utilized type I collagen gel tissue-equivalents (TEs) as a simplified model system to evaluate properties and relationships of tissue components. TEs are particularly useful because organizational and compositional properties can be controlled during formulation (e.g., mold geometry altered to induce changes in collagen fiber alignment [3]). While our other work has used co-gel tissue analogs to evaluate the contribution of non-fibrillar matrix to indentation [4], the purpose of this study was to evaluate the role of initial collagen organization on tissue behavior in indentation using cell-compacted TEs as a model system.

scholarly journals Microscale Fiber Network Alignment Affects Macroscale Failure Behavior in Simulated Collagen Tissue Analogs

2013 ◽  
Vol 135 (2) ◽  
Author(s):  
Mohammad F. Hadi ◽  
Victor H. Barocas
Keyword(s):  
Type I Collagen ◽  
Soft Tissues ◽  
Collagen Gel ◽  
Aortic Aneurysms ◽  
Failure Behavior ◽  
Fe Model ◽  
Type I ◽  
Fiber Network ◽  
Fiber Alignment ◽  
Damage And Failure

A tissue's microstructure determines its failure properties at larger length scales, however, the specific relationship between microstructure and macroscopic failure in native and engineered soft tissues (such as capsular ligaments, aortic aneurysms, or vascular grafts) has proven elusive. In this study, variations in the microscale fiber alignment in collagen gel tissue analogs were modeled in order to understand their effects on macroscale damage and failure outcomes. The study employed a multiscale finite-element (FE) model for damage and failure in collagen-based materials. The model relied on microstructural representative volume elements (RVEs) that consisted of stochastically-generated networks of discrete type-I collagen fibers. Fiber alignment was varied within RVEs and between layers of RVEs in a macroscopic FE model of a notched dogbone geometry. The macroscale stretch and the microscale response of fibers for each of the differently aligned cases were compared as the dogbone was uniaxially extended to failure. Networks with greater fiber alignment parallel to the direction of extension failed at smaller strains (with a 6–22% reduction in the Green strain at failure), however, at greater grip forces (a 28–60% increase) than networks with fibers aligned perpendicular to the extension. Alternating layers of crisscrossed network alignments (aligned ±45 deg to the direction of extension) failed at smaller strains but at greater grip forces than those created using one fiber alignment type. In summary, variations in microscale structure via fiber alignment produced different macroscale failure trends. To conclude, these findings may be significant in the realm of tissue engineering and in soft tissue biomechanics.

Type I collagen permits invasive behaviour by retinal pigmented epithelial cells in vitro

1987 ◽  
Vol 87 (3) ◽  
pp. 399-409
Author(s):  
R.J. Docherty ◽  
J.V. Forrester ◽  
J.M. Lackie
Keyword(s):  
Epithelial Cells ◽  
Type I Collagen ◽  
Phenotypic Expression ◽  
Type I ◽  
Collagen Gels ◽  
Rpe Cells ◽  
Dome Formation ◽  
Type Iv

Epithelial cells cultured on type I collagen gels adopt a typical apical—basal polarity and undergo differentiation. We have compared the behaviour of chick embryo retinal pigmented epithelial (RPE) cells on collagen and on plastic with and without gelatin coats. RPE cell proliferation was similar on all three substrata, and post-confluent cultures exhibited multilayering. On plastic and gelatin-coated plastic, dome formation, typical of transporting epithelia, occurred. On type I collagen gels, however, dome formation did not occur, but rather invasion of the gel matrix by cords of epithelial cells took place. In contrast, invasive behaviour of the cells was markedly reduced on type IV coated collagen gels, particularly in the presence of laminin. These results illustrate the prominent role of the extracellular matrix on phenotypic expression by RPE cells and may represent a more general phenomenon.

scholarly journals The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cell Metabolism ◽  
Breast Tumors ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Desmoplastic Reaction ◽  
The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

Type I collagen from sea cucumber (Stichopus japonicus) and the role of matrix metalloproteinase-2 in autolysis

2021 ◽  
Vol 41 ◽  
pp. 100959
Author(s):  
Long-Jie Yan ◽  
Le-Chang Sun ◽  
Kai-Yuan Cao ◽  
Yu-Lei Chen ◽  
Ling-Jing Zhang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Sea Cucumber ◽  
Type I Collagen ◽  
Matrix Metalloproteinase 2 ◽  
Type I ◽  
Stichopus Japonicus

Role of the amino-terminal extrahelical region of type I collagen in directing the 4D overlap in fibrillogenesis

Biopolymers ◽  
1979 ◽  
Vol 18 (12) ◽  
pp. 3005-3014 ◽  
Author(s):  
Donald L. Helseth ◽  
Joseph H. Lechner ◽  
Arthur Veis
Keyword(s):  
Type I Collagen ◽  
Type I ◽  
Amino Terminal
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