Extracellular Matrix Elasticity Modulates TGF-β–Induced p38 Activation and Myofibroblast Transdifferentiation in Human Tenon Fibroblasts

2011 ◽  
Vol 52 (12) ◽  
pp. 9149 ◽  
Author(s):  
Tobias Meyer-ter-Vehn ◽  
Hong Han ◽  
Franz Grehn ◽  
Günther Schlunck
2016 ◽  
Vol 4 (1) ◽  
pp. 9-26 ◽  
Author(s):  
Fengxuan Han ◽  
Caihong Zhu ◽  
Qianping Guo ◽  
Huilin Yang ◽  
Bin Li

The elasticity of the extracellular matrix has been increasingly recognized as a dominating factor of cell fate and activities. This review provides an overview of the general principles and recent advances in the field of matrix elasticity-dependent regulation of a variety of cellular activities and functions, the underlying biomechanical and molecular mechanisms, as well as the pathophysiological implications.


Author(s):  
Tomoya KOMATSU ◽  
Ryo SUDO ◽  
Toshiihro MITAKA ◽  
Mariok IKEDA ◽  
Kazuo TANISHITA

2014 ◽  
Vol 306 (11) ◽  
pp. H1525-H1539 ◽  
Author(s):  
Megan L. McCain ◽  
Hongyan Yuan ◽  
Francesco S. Pasqualini ◽  
Patrick H. Campbell ◽  
Kevin Kit Parker

Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis, and decreased myocyte length-to-width aspect ratio. Ventricular thickening is considered compensatory because it reduces wall stress, but the functional consequences of cell shape remodeling in this pathological setting are unknown. We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize contractility when the extracellular matrix becomes stiffer due to conditions such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin alignment was unaffected by matrix elasticity, but sarcomere content was typically higher on stiff gels. Microtubule polymerization was higher on stiff gels, implying increased intracellular elastic modulus. On moderate gels, myocytes with moderate aspect ratios (∼7:1) generated the most peak systolic work compared with other cell shapes. However, on stiffer gels, low aspect ratios (∼2:1) generated the most peak systolic work. To compare the relative contributions of intracellular vs. extracellular elasticity to contractility, we developed an analytical model and used our experimental data to fit unknown parameters. Our model predicted that matrix elasticity dominates over intracellular elasticity, suggesting that the extracellular matrix may potentially be a more effective therapeutic target than microtubules. Our data and model suggest that myocytes with lower aspect ratios have a functional advantage when the elasticity of the extracellular matrix decreases due to conditions such as fibrosis, highlighting the role of the extracellular matrix in cardiac disease.


2005 ◽  
Vol 2004.17 (0) ◽  
pp. 269-270
Author(s):  
Nahoko YAMAMURA ◽  
Akinori UEDA ◽  
Ryo SUDO ◽  
Mariko IKEDA ◽  
Kazuo TANISHITA

2014 ◽  
Vol 106 (2) ◽  
pp. 572a
Author(s):  
Medha M. Pathak ◽  
Jamison L. Nourse ◽  
Truc Tran ◽  
Janahan Arulmoli ◽  
Lisa A. Flanagan ◽  
...  

2017 ◽  
Vol 313 (4) ◽  
pp. H757-H767 ◽  
Author(s):  
Davi M. Lyra-Leite ◽  
Allen M. Andres ◽  
Andrew P. Petersen ◽  
Nethika R. Ariyasinghe ◽  
Nathan Cho ◽  
...  

Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease. NEW & NOTEWORTHY A new methodology has been developed to measure O2 consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix elasticity regulates basal mitochondrial function, whereas both matrix elasticity and tissue alignment regulate mitochondrial stress responses.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Mateusz M. Urbanski ◽  
Lyle Kingsbury ◽  
Daniel Moussouros ◽  
Imran Kassim ◽  
Saraf Mehjabeen ◽  
...  

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