scholarly journals The role of cell-matrix interactions in connective tissue mechanics

2021 ◽  
Author(s):  
Iain Muntz ◽  
Michele Fenu ◽  
Gerjo J V M van Osch ◽  
Gijsje Koenderink

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.

1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.


1993 ◽  
Vol 11 (S1) ◽  
pp. S112-S114 ◽  
Author(s):  
M. Baccarani Contri ◽  
R. Tiozzo ◽  
M. A. Croce ◽  
T. Andreoli ◽  
A. De Paepe

2021 ◽  
Author(s):  
Lewis S. Gaffney ◽  
Matthew B. Fisher ◽  
Donald O. Freytes

AbstractMuscle and tendon injuries are prevalent and range from minor sprains and strains to traumatic, debilitating injuries. However, the interactions between these tissues during injury and recovery remain unclear. Three-dimensional tissue models that incorporate both tissues and a physiologically relevant junction between muscle and tendon may aide in understanding how the two tissues interact. Here, we use tissue specific extracellular matrix (ECM) derived from muscle and tendon to determine how cells of each tissue interact with the microenvironment of the opposite tissue resulting in junction specific features. ECM materials were derived from the achilles tendon and gastrocnemius muscle, decellularized, and processed to form tissue specific pre-hydrogel digests. C2C12 myoblasts and tendon fibroblasts were cultured in tissue-specific ECM conditioned media or encapsulated in tissue-specific ECM hydrogels to determine cell-matrix interactions and the effects on a muscle-tendon junction marker, paxillin. ECM conditioned media had only a minor effect on upregulation of paxillin in cells cultured in monolayer. However, cells cultured within ECM hydrogels had 50-70% higher paxillin expression than cells cultured in type I collagen hydrogels. Contraction of the ECM hydrogels varied by the type of ECM used. Subsequent experiments with varying density of type I collagen (and thus contraction) showed no correlation between paxillin expression and the amount of gel contraction, suggesting that a constituent of the ECM was the driver of paxillin expression in the ECM hydrogels. Using tissue specific ECM allowed for the de-construction of the cell-matrix interactions similar to muscle-tendon junctions to study the expression of MTJ specific proteins.Impact StatementThe muscle-tendon junction is an important feature of muscle-tendon units; however, despite cross-talk between the two tissue types, it is overlooked in current research. Deconstructing the cell-matrix interactions will allow the opportunity to study significant junction specific features and markers that should be included in tissue models of the muscle-tendon unit, while gaining a deeper understanding of the natural junction. This research aims to inform future methods to engineer a more relevant multi-tissue platform to study the muscle-tendon unit.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Juliane Winkler ◽  
Abisola Abisoye-Ogunniyan ◽  
Kevin J. Metcalf ◽  
Zena Werb

Abstract Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions and ECM remodelling. Tumours leverage ECM remodelling to create a microenvironment that promotes tumourigenesis and metastasis. In this review, we focus on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumour-associated ECM. These tumour-driven changes support tumour growth, increase migration of tumour cells, and remodel the ECM in distant organs to allow for metastatic progression. A better understanding of the underlying mechanisms of tumourigenic ECM remodelling is crucial for developing therapeutic treatments for patients.


2021 ◽  
Vol 17 (2) ◽  
pp. 149-168
Author(s):  
Jiapeng Yang ◽  
Yu Zhang ◽  
Meng Qin ◽  
Wei Cheng ◽  
Wei Wang ◽  
...  

Similar to natural tissues, hydrogels contain abundant water, so they are considered as promising biomaterials for studying the influence of the mechanical properties of extracellular matrices (ECM) on various cell functions. In recent years, the growing research on cellular mechanical response has revealed that many cell functions, including cell spreading, migration, tumorigenesis and differentiation, are related to the mechanical properties of ECM. Therefore, how cells sense and respond to the extracellular mechanical environment has gained considerable attention. In these studies, hydrogels are widely used as the in vitro model system. Hydrogels of tunable stiffness, viscoelasticity, degradability, plasticity, and dynamical properties have been engineered to reveal how cells respond to specific mechanical features. In this review, we summarize recent process in this research direction and specifically focus on the influence of the mechanical properties of the ECM on cell functions, how cells sense and respond to the extracellular mechanical environment, and approaches to adjusting the stiffness of hydrogels.


1991 ◽  
Vol 19 (2) ◽  
pp. 187S-187S ◽  
Author(s):  
ANTHONY J SMITH ◽  
ROSALIND S TOBIAS ◽  
CLIVE G PLANT ◽  
ROGER M BROWNE ◽  
HERVE LESOT ◽  
...  

Author(s):  
Jinglei Wu ◽  
Jiazhu Xu ◽  
Yi-hui Huang ◽  
Liping Tang ◽  
Yi Hong

Abstract Decellularized meniscal extracellular matrix (ECM) material holds great potential for meniscus repair and regeneration. Particularly, injectable ECM hydrogel is highly desirable for the minimally invasive treatment of irregularly shaped defects. Although regional-specific variations of the meniscus are well documented, no ECM hydrogel has been reported to simulate zonally specific microenvironments of the native meniscus. To fill the gap, different (outer, middle, and inner) zones of porcine menisci were separately decellularized. Then the regionally decellularized meniscal ECMs were solubilized by pepsin digestion, neutralized, and then form injectable hydrogels. The hydrogels were characterized in gelation behaviors and mechanical properties and seeded with bovine fibrochondrocytes to evaluate the regionally biochemical effects on the cell-matrix interactions. Our results showed that the decellularized inner meniscal ECM (IM) contained the greatest glycosaminoglycan (GAG) content and the least collagen content compared with the decellularized outer meniscal ECM (OM) and middle meniscal ECM (MM). The IM hydrogel showed lower compressive strength than the OM hydrogel. When encapsulated with fibrochondrocytes, the IM hydrogel accumulated more GAG, contracted to a greater extent and reached higher compressive strength than that of the OM hydrogel at 28 days. Our findings demonstrate that the regionally specific meniscal ECMs present biochemical variation and show various effects on the cell behaviors, thus providing information on how meniscal ECM hydrogels may be utilized to reconstruct the microenvironments of the native meniscus.


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