scholarly journals Extra-cellular matrix in multicellular aggregates acts as a pressure sensor controlling cell proliferation and motility

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Monika E Dolega ◽  
Sylvain Monnier ◽  
Benjamin Brunel ◽  
Jean-François Joanny ◽  
Pierre Recho ◽  
...  

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions. To perceive mechanical perturbations of different types and magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results of selective osmotic compressions of CT26 cells within multicellular aggregates and global aggregate compressions, we show that global compressions have a strong impact on the aggregates growth and internal cell motility, while selective compressions of same magnitude have almost no effect. Both compressions alter the volume of individual cells in the same way over a shor-timescale, but, by draining the water out of the extracellular matrix, the global one imposes a residual compressive mechanical stress on the cells over a long-timescale, while the selective one does not. We conclude that the extracellular matrix is as a sensor that mechanically regulates cell proliferation and migration in a 3D environment.

2020 ◽  
Author(s):  
Monika E. Dolega ◽  
Sylvain Monnier ◽  
Benjamin Brunel ◽  
Jean-François Joanny ◽  
Pierre Recho ◽  
...  

AbstractImposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions. To perceive mechanical perturbations of different types and magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results of selective osmotic compressions of cells within multicellular aggregates with small osmolites and global aggregate compressions with big osmolites, we show that global compressions have a strong impact on the aggregates growth and internal cell motility, while selective compressions of same magnitude have almost no effect. Both compressions alter the volume of individual cells in the same way but, by draining the water out of the extracellular matrix, the global one imposes a residual compressive mechanical stress on the cells while the selective one does not. We conclude that, in aggregates, the extracellular matrix is as a sensor which mechanically regulates cell proliferation and migration in a 3D environment.


2018 ◽  
Author(s):  
Monika E. Dolega ◽  
Benjamin Brunel ◽  
Magali Le Goff ◽  
Magdalena Greda ◽  
Claude Verdier ◽  
...  

AbstractImposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions 1–5. To perceive mechanical perturbations of different types and magnitudes, tissues need a range of appropriate detectors 6–8, with a compliance that has to match the perturbation amplitude. As a proxy of biological tissues, we use multicellular aggregates, a composite material made of cells, extracellular matrix and permeating fluid. We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9–13, while the same amount of selective compression on cells has almost no effect 14,15. We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space. This description correctly predicts the emergent bulk modulus of the aggregate as well as the hydrodynamic diffusion coefficient of the percolating interstitial fluid under compression. We further show that, on a longer timescale, the extracellular matrix serves as a sensor that regulates cell proliferation and migration in a 3D environment through its permanent deformation and dehydration following the global compression.


2021 ◽  
Vol 7 (1) ◽  
pp. 7
Author(s):  
Irene Abelenda Núñez ◽  
Ramón G. Rubio ◽  
Francisco Ortega ◽  
Eduardo Guzmán

Hydrogels (HG) are 3D networks of hydrophilic macromolecules linked by different “cross-linking points”, which have as a main advantage their capacity for the adsorption of large amounts of water without any apparent dissolution. This allows hydrogels to undergo reversible swelling–shrinking processes upon the modification of the environmental conditions (pH, ionic strength or temperature). This stimuli-responsiveness and their ability for entrapping in their interior different types of molecules makes hydrogels suitable platforms for drug delivery applications. Furthermore, HGs exhibit certain similarities to the extracellular tissue matrix and can be used as a support for cell proliferation and migration.


2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Wei Cao ◽  
Youping Feng

Abstract Background Long noncoding RNAs (lncRNAs) have been reported to be associated with dermis process during burn wound healing. This study aimed to investigate the role of lncRNA X-inactive specific transcript (XIST) in human skin fibroblasts (HSF) and extracellular matrix (ECM) as well as the regulatory network of XIST/microRNA-29b-3p (miR-29b-3p)/collagen 1 alpha 1 (COL1A1). Methods The wound samples were collected from 25 patients with deep partial thickness burn at day 5 after burn. The thermal injured model was established using HSF cells. The expressions of XIST, miR-29b-3p and COL1A1 were measured by quantitative real-time polymerase chain reaction and western blot. ECM synthesis, cell proliferation and migration were detected by western blot, cell counting kit-8 and trans-well assays, respectively. The interaction between miR-29b-3p and XIST or COL1A1 was explored by bioinformatics analysis and luciferase reporter assay. Results The expressions of XIST and COL1A1 were enhanced but miR-29b-3p expression was decreased after thermal injury. XIST overexpression promoted ECM synthesis, cell proliferation and migration in thermal injured HSF cells. However, XIST knockdown played an opposite effect. miR-29b-3p overexpression inhibited ECM synthesis, cell proliferation and migration, which was reversed by XIST. COL1A1 silence suppressed ECM synthesis, cell proliferation and migration by miR-29b-3p targeting. Moreover, COL1A1 up-regulation weakened the effect of XIST silence on ECM synthesis and HSF cell function. Conclusion XIST promoted ECM synthesis, cell proliferation and migration by sponging miR-29b-3p and targeting COL1A1 in HSF cells after thermal injury, indicating the promoting role of XIST in wound healing.


2020 ◽  
Vol 17 (3) ◽  
pp. 147916412090797 ◽  
Author(s):  
Dorothee Weihrauch ◽  
Dustin P Martin ◽  
Deron Jones ◽  
John Krolikowski ◽  
Janine Struve ◽  
...  

Objective: Diabetes mellitus is a significant risk factor for peripheral artery disease. Diabetes mellitus induces chronic states of oxidative stress and vascular inflammation that increase neutrophil activation and release of myeloperoxidase. The goal of this study is to determine whether inhibiting myeloperoxidase reduces oxidative stress and neutrophil infiltration, increases vascularization, and improves blood flow in a diabetic murine model of hindlimb ischaemia. Methods: Leptin receptor–deficient ( db/db) mice were subjected to hindlimb ischaemia. Ischaemic mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC) to inhibit myeloperoxidase. After ligating the femoral artery, effects of treatments were determined with respect to hindlimb blood flow, neutrophil infiltration, oxidative damage, and the capability of hindlimb extracellular matrix to support human endothelial cell proliferation and migration. Results: KYC treatment improved hindlimb blood flow at 7 and 14 days in db/db mice; decreased the formation of advanced glycation end products, 4-hydroxynonenal, and 3-chlorotyrosine; reduced neutrophil infiltration into the hindlimbs; and improved the ability of hindlimb extracellular matrix from db/db mice to support endothelial cell proliferation and migration. Conclusion: These results demonstrate that inhibiting myeloperoxidase reduces oxidative stress in ischaemic hindlimbs of db/db mice, which improves blood flow and reduces neutrophil infiltration such that hindlimb extracellular matrix from db/db mice supports endothelial cell proliferation and migration.


Development ◽  
1954 ◽  
Vol 2 (2) ◽  
pp. 114-121
Author(s):  
G. A. Thomas

The effect of cortisone on the proliferation of tissues other than mesenchymal has received little attention. Bullough (1952) showed that cortisone had a marked effect on the mitotic activity of the epidermis in mice, and Leroy (1952) showed a similar effect on immature testes of rats, but no effect on mature ones. McColl & Weston (1953) have studied the influence of cortisone on the process of Wallerian degeneration in peripheral nerve and noted that there was less total cellularity in degenerated nerves from cortisone-treated animals. It was thought useful to undertake a quantitative study of proliferation during Wallerian degeneration in peripheral nerves from cortisone-treated animals because the normal changes in nuclear population during this process have been intensively investigated (Abercrombie & Johnson, 1946; Thomas, 1948), and it is known that different types of cells multiply at different rates.


Development ◽  
2001 ◽  
Vol 128 (13) ◽  
pp. 2485-2496 ◽  
Author(s):  
Emmanuel Garcion ◽  
Andreas Faissner ◽  
Charles ffrench-Constant

The extracellular matrix glycoprotein tenascin-C is widely expressed in the vertebrate central nervous system (CNS) during development and repair. Despite multiple effects of tenascin-C on cell behaviour in culture, no structural abnormalities of the CNS and other organs have been found in adult tenascin-C-null mice, raising the question of whether this glycoprotein has a significant role in vivo. Using a transgenic approach, we have demonstrated that tenascin-C regulates both cell proliferation and migration in oligodendrocyte precursors during development. Knockout mice show increased rates of oligodendrocyte precursor migration along the optic nerve and reduced rates of oligodendrocyte precursor proliferation in different regions of the CNS. Levels of programmed cell death were reduced in areas of myelination at later developmental stages,providing a potential corrective mechanism for any reduction in cell numbers that resulted from the proliferation phenotype. The effects on cell proliferation are mediated via the αvβ3 integrin and an interaction with the platelet-derived growth factor-stimulated mitogenic pathway, emphasising the importance of both CNS extracellular matrix and integrin growth factor interactions in the regulation of neural precursor behaviour.


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