Physical and functional cell-matrix uncoupling in a developing tissue under tension

AbstractTissue mechanics play a crucial role in organ development. It relies on cells and extracellular matrix (ECM) mechanical properties, but also on their reciprocal interaction. The relative physical contribution of cells and ECM to morphogenesis is poorly understood. Here, we dissected the mechanics of the envelope of the Drosophila developing leg, an epithelium submitted to a number of mechanical stresses: first stretched, it is then torn apart and withdrawn to free the leg. During stretching, we found that mechanical tension is entirely borne by the ECM at first, then by the cellular monolayer as soon as they detach themselves from one another. Then, each envelope layer is removed by an independent mechanism: while ECM withdraws following local proteolysis, cellular monolayer withdrawal is independent of ECM degradation and driven by an autonomous myosin-II-dependent contraction. These results reveal a physical and functional cell-matrix uncoupling that could timely control tissue dynamics during development.

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The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00111.2013 ◽

2013 ◽

Vol 305 (12) ◽

pp. E1427-E1435 ◽

Cited By ~ 104

Author(s):

Nadia Alkhouli ◽

Jessica Mansfield ◽

Ellen Green ◽

James Bell ◽

Beatrice Knight ◽

...

Keyword(s):

Mechanical Properties ◽

Extracellular Matrix ◽

Stress Relaxation ◽

Time Course ◽

Tissue Mechanics ◽

Cellular Growth ◽

Nonlinear Microscopy ◽

Force Extension ◽

Ecm Remodeling ◽

Nonlinear Stress

Adipose tissue (AT) expansion in obesity is characterized by cellular growth and continuous extracellular matrix (ECM) remodeling with increased fibrillar collagen deposition. It is hypothesized that the matrix can inhibit cellular expansion and lipid storage. Therefore, it is important to fully characterize the ECM's biomechanical properties and its interactions with cells. In this study, we characterize and compare the mechanical properties of human subcutaneous and omental tissues, which have different physiological functions. AT was obtained from 44 subjects undergoing surgery. Force/extension and stress/relaxation data were obtained. The effects of osmotic challenge were measured to investigate the cellular contribution to tissue mechanics. Tissue structure and its response to tensile strain were determined using nonlinear microscopy. AT showed nonlinear stress/strain characteristics of up to a 30% strain. Comparing paired subcutaneous and omental samples ( n = 19), the moduli were lower in subcutaneous: initial 1.6 ± 0.8 (means ± SD) and 2.9 ± 1.5 kPa ( P = 0.001), final 11.7 ± 6.4 and 32 ± 15.6 kPa ( P < 0.001), respectively. The energy dissipation density was lower in subcutaneous AT ( n = 13): 0.1 ± 0.1 and 0.3 ± 0.2 kPa, respectively ( P = 0.006). Stress/relaxation followed a two-exponential time course. When the incubation medium was exchanged for deionized water in specimens held at 30% strain, force decreased by 31%, and the final modulus increased significantly. Nonlinear microscopy revealed collagen and elastin networks in close proximity to adipocytes and a larger-scale network of larger fiber bundles. There was considerable microscale heterogeneity in the response to strain in both cells and matrix fibers. These results suggest that subcutaneous AT has greater capacity for expansion and recovery from mechanical deformation than omental AT.

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Lung tissue mechanics and extracellular matrix composition in a murine model of silicosis

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.4.1400 ◽

2001 ◽

Vol 90 (4) ◽

pp. 1400-1406 ◽

Cited By ~ 47

Author(s):

Débora S. Faffe ◽

Gabriela H. Silva ◽

Pedro M. P. Kurtz ◽

Elnara M. Negri ◽

Vera L. Capelozzi ◽

...

Keyword(s):

Mechanical Properties ◽

Extracellular Matrix ◽

Lung Tissue ◽

Elastic System ◽

Elastic Fiber ◽

Dynamic Mechanical Properties ◽

Tissue Mechanics ◽

Matrix Composition ◽

Elastic Fibers ◽

Oxytalan Fibers

The dynamic mechanical properties of lung tissue and its contents of collagen and elastic fibers were studied in strips prepared from mice instilled intratracheally with saline (C) or silica [15 (S15) and 30 days (S30) after instillation]. Resistance, elastance, and hysteresivity were studied during oscillations at different frequencies on S15 and S30. Elastance increased from C to silica groups but was similar between S15 and S30. Resistance was augmented from C to S15 and S30 and was greater in S30 than in S15 at higher frequencies. Hysteresivity was higher in S30 than in C and S15. Silica groups presented a greater amount of collagen than did C. Elastic fiber content increased progressively along time. This increment was related to the higher amount of oxytalan fibers at 15 and 30 days, whereas elaunin and fully developed elastic fibers were augmented only at 30 days. Silicosis led not only to pulmonary fibrosis but also to fibroelastosis, thus assigning a major role to the elastic system in the silicotic lung.

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Biohybrid Fibro-Porous Vascular Scaffolds: Effect of Crosslinking on Properties

MRS Proceedings ◽

10.1557/opl.2015.490 ◽

2015 ◽

Vol 1718 ◽

pp. 79-84 ◽

Cited By ~ 4

Author(s):

Vinoy Thomas ◽

Danna Nozik ◽

Harsh Patel ◽

Raj K. Singh ◽

Yogesh K. Vohra

Keyword(s):

Mechanical Properties ◽

Extracellular Matrix ◽

Diameter Distribution ◽

Sem Images ◽

Cell Matrix ◽

Matrix Interactions ◽

Fiber Size ◽

Vascular Scaffolds ◽

Cell Matrix Interactions ◽

Crosslinking Agents

ABSTRACTTubular grafts were fabricated from blends of polycaprolactone (PCL) and poly(glycolide-co-caprolactone) (PGC) polymers and coated with an extracellular matrix containing collagens, laminin, and proteoglycans, but not growth factors (HuBiogel™). Multifunctional scaffolds from polymer blends and membrane proteins provide the necessary biomechanics and biological functions for tissue regeneration. Two crosslinking agents, a natural crosslinker namely genipin (Gp) and a carbodiimide reagent namely 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), were used for further stabilizing the protein matrix and the effect of crosslinking was evaluated for structural, morphological, mechanical properties using SEM, DSC and DMA. SEM images and fiber diameter distribution showed fiber-size between 0.2 μm to 1 μm with the majority of fiber diameters being under 500 nm, indicating upper range of protein fiber-sizes (for example, collagen fibers in extracellular matrix are in 50 to 500 nm diameter range). HB coating did not affect the mechanical properties, but increased its hydrophilicity of the graft. Overall data showed that PCL/PGC blends with 3:1 mass ratio exhibited mechanical properties comparable to those of human native arteries (tensile strength of 1-2 MPa and Young’s modulus of <10 MPa). Additionally, the effect of crosslinking on coating stability was investigated to assure the retention of proteins on scaffold for effective cell-matrix interactions.

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Extracellular Matrix in Cardiac Tissue Mechanics and Physiology: Role of Collagen Accumulation

10.5772/intechopen.96585 ◽

2021 ◽

Author(s):

Kristen LeBar ◽

Zhijie Wang

Keyword(s):

Heart Failure ◽

Mechanical Properties ◽

Extracellular Matrix ◽

Pressure Overload ◽

Volume Overload ◽

Tissue Mechanics ◽

Functional Changes ◽

Collagen Accumulation ◽

Heart Failure Progression

The extracellular matrix (ECM) forms a mesh surrounding tissue, made up of fibrous and non-fibrous proteins that contribute to the cellular function, mechanical properties of the tissue and physiological function of the organ. The cardiac ECM remodels in response to mechanical alterations (e.g., pressure overload, volume overload) or injuries (e.g., myocardial infarction, bacterial infection), which further leads to mechanical and functional changes of the heart. Collagen, the most prevalent ECM protein in the body, contributes significantly to the mechanical behavior of myocardium during disease progression. Alterations in collagen fiber morphology and alignment, isoform, and cross-linking occur during the progression of various cardiac diseases. Acute or compensatory remodeling of cardiac ECM maintains normal cardiac function. However, chronic or decompensatory remodeling eventually results in heart failure, and the exact mechanism of transition into maladaptation remains unclear. This review aims to summarize the primary role of collagen accumulation (fibrosis) in heart failure progression, with a focus on its effects on myocardial tissue mechanical properties and cellular and organ functions.

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Probing cellular response to topography in three dimensions

10.1101/232066 ◽

2017 ◽

Author(s):

Colin D. Paul ◽

Alex Hruska ◽

Jack R. Staunton ◽

Hannah A. Burr ◽

Kathryn M. Daly ◽

...

Keyword(s):

Mechanical Properties ◽

Cellular Response ◽

Colloidal Particles ◽

Myosin Ii ◽

Tissue Mechanics ◽

Three Dimensions ◽

Cell Alignment ◽

Ecm Proteins ◽

Aligned Fibers

ABSTRACTBiophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, and architecture or topography of the extracellular matrix (ECM). These aspects act in concert with chemical signals from a myriad of diverse ECM proteins to provide cues that drive cellular responses. Here, we used a bottom-up approach to build fibrillar architecture into 3D amorphous hydrogels using magnetic-field driven assembly of paramagnetic colloidal particles functionalized with three types of human ECM proteins found in vivo. We investigated if cells cultured in matrices comprised of fibrils of the same size and arranged in similar geometries will show similar behavior for each of the ECM proteins tested. We were able to resolve spatial heterogeneities in microscale mechanical properties near aligned fibers that were not observed in bulk tissue mechanics. We then used this platform to examine factors contributing to cell alignment in response to topographical cues in 3D laminin-rich matrices. Multiple human cell lines extended protrusions preferentially in directions parallel or perpendicular to aligned fibers independently of the ECM coating. Focal adhesion proteins, as measured by paxillin localization, were mainly diffuse in the cytoplasm, with few puncta localized at the protrusions. Integrin β1 and fascin regulated protrusion extension but not protrusion alignment. Myosin II inhibition did not reduce observed protrusion length. Instead, cells with reduced myosin II activity generated protrusions in random orientations when cultured in hydrogels with aligned fibers. Similarly, myosin II dependence was observed in vivo, where cells no longer aligned along the abluminal surfaces of blood vessels upon treatment with blebbistatin. These data suggest that myosin II can regulate sensing of topography in 3D engineered matrices for both normal and transformed cells.

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The role of cell-matrix interactions in connective tissue mechanics

Physical Biology ◽

10.1088/1478-3975/ac42b8 ◽

2021 ◽

Author(s):

Iain Muntz ◽

Michele Fenu ◽

Gerjo J V M van Osch ◽

Gijsje Koenderink

Keyword(s):

Extracellular Matrix ◽

Connective Tissue ◽

Connective Tissue Diseases ◽

Tissue Mechanics ◽

Cell Matrix ◽

Matrix Interactions ◽

Sense And Respond ◽

Contractile Forces ◽

Cell Matrix Interactions ◽

Extracellular Environment

Abstract Living tissue is able to withstand large stresses in everyday life, yet it also actively adapts to dynamic loads. This remarkable mechanical behaviour emerges from the interplay between living cells and their non-living extracellular environment. Here we review recent insights into the biophysical mechanisms involved in the reciprocal interplay between cells and the extracellular matrix and how this interplay determines tissue mechanics, with a focus on connective tissues. We first describe the roles of the main macromolecular components of the extracellular matrix in regards to tissue mechanics. We then proceed to highlight the main routes via which cells sense and respond to their biochemical and mechanical extracellular environment. Next we introduce the three main routes via which cells can modify their extracellular environment: exertion of contractile forces, secretion and deposition of matrix components, and matrix degradation. Finally we discuss how recent insights in the mechanobiology of cell-matrix interactions are furthering our understanding of the pathophysiology of connective tissue diseases and cancer, and facilitating the design of novel strategies for tissue engineering.

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Age related extracellular matrix and interstitial cell phenotype in pulmonary valves

Scientific Reports ◽

10.1038/s41598-020-78507-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Shaohua Wu ◽

Vikas Kumar ◽

Peng Xiao ◽

Mitchell Kuss ◽

Jung Yul Lim ◽

...

Keyword(s):

Mechanical Properties ◽

Extracellular Matrix ◽

Heart Valve ◽

Cell Phenotype ◽

Primary Concern ◽

Ross Operation ◽

Extracellular Matrix Components ◽

Matrix Components

AbstractHeart valve disease is a common manifestation of cardiovascular disease and is a significant cause of cardiovascular morbidity and mortality worldwide. The pulmonary valve (PV) is of primary concern because of its involvement in common congenital heart defects, and the PV is usually the site for prosthetic replacement following a Ross operation. Although effects of age on valve matrix components and mechanical properties for aortic and mitral valves have been studied, very little is known about the age-related alterations that occur in the PV. In this study, we isolated PV leaflets from porcine hearts in different age groups (~ 4–6 months, denoted as young versus ~ 2 years, denoted as adult) and studied the effects of age on PV leaflet thickness, extracellular matrix components, and mechanical properties. We also conducted proteomics and RNA sequencing to investigate the global changes of PV leaflets and passage zero PV interstitial cells in their protein and gene levels. We found that the size, thickness, elastic modulus, and ultimate stress in both the radial and circumferential directions and the collagen of PV leaflets increased from young to adult age, while the ultimate strain and amount of glycosaminoglycans decreased when age increased. Young and adult PV had both similar and distinct protein and gene expression patterns that are related to their inherent physiological properties. These findings are important for us to better understand the physiological microenvironments of PV leaflet and valve cells for correctively engineering age-specific heart valve tissues.

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Mechanical properties of decellularized extracellular matrix coated with TiCaPCON film

Biomedical Materials ◽

10.1088/1748-605x/aa6fc0 ◽

2017 ◽

Vol 12 (3) ◽

pp. 035014 ◽

Cited By ~ 8

Author(s):

I V Sukhorukova ◽

A N Sheveyko ◽

K L Firestein ◽

Ph V Kiryukhantsev-Korneev ◽

D Golberg ◽

...

Keyword(s):

Mechanical Properties ◽

Extracellular Matrix ◽

Decellularized Extracellular Matrix

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A Multiscale Approach to Modeling the Passive Mechanical Contribution of Cells in Tissues

Volume 1B: Extremity; Fluid Mechanics; Gait; Growth, Remodeling, and Repair; Heart Valves; Injury Biomechanics; Mechanotransduction and Sub-Cellular Biophysics; MultiScale Biotransport; Muscle, Tendon and Ligament; Musculoskeletal Devices; Multiscale Mechanics; Thermal Medicine; Ocular Biomechanics; Pediatric Hemodynamics; Pericellular Phenomena; Tissue Mechanics; Biotransport Design and Devices; Spine; Stent Device Hemodynamics; Vascular Solid Mechanics; Student Paper and Design Competitions ◽

10.1115/sbc2013-14533 ◽

2013 ◽

Author(s):

Victor K. Lai ◽

Mohammad F. Hadi ◽

Robert T. Tranquillo ◽

Victor H. Barocas

Keyword(s):

Extracellular Matrix ◽

Soft Tissues ◽

Multiscale Model ◽

Tissue Mechanics ◽

Multiscale Approach ◽

Cellular Solids ◽

Comprehensive Model ◽

Modeling Framework ◽

Tissue Biomechanics ◽

Tensegrity Model

In addition to their obvious biological roles in tissue function, cells often play a significant mechanical role through a combination of passive and active behaviors. Phenomenological and continuum modeling approaches to understand tissue biomechanics have included improved constitutive laws that incorporate anisotropy in the extracellular matrix (ECM) and/or cellular phenomenon, e.g, [1]. The lack of microstructural detail in these models, however, limits their ability to explore the respective contributions and interactions between different components within a tissue. In contrast, structural approaches attempt to understand tissue biomechanics by incorporating microstructural details directly into the model, e.g., the tensegrity model [2], cellular solids models [3], or biopolymer models [4]. Research in our group focuses on developing a comprehensive model to predict the mechanical behavior of soft tissues via a multiscale approach, a technique that allows integration of the microstructural details of different components into the modeling framework. A significant gap in our previous models, however, is the absence of cells. The current work represents an improvement of the multiscale model via the addition of cells, and investigates the passive mechanical contribution of cells to overall tissue mechanics.

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