scholarly journals Extracellular Matrix acts as pressure detector in biological tissues

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.

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.


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.


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.


2020 ◽  
Author(s):  
Lungwani Muungo

ADP ribosylation factor GTPase-activating protein 3 (ARFGAP3) is a GTPase-activating protein that associates with the Golgiapparatus and regulates the vesicular trafficking pathway. In the present study, we examined the contribution of ARFGAP3 toprostate cancer cell biology. We showed that ARFGAP3 expression was induced by 100 nM of dihydrotestosterone (DHT) atboth the mRNA and protein levels in androgen-sensitive LNCaP cells. We generated stable transfectants of LNCaP cells withFLAG-tagged ARFGAP3 or a control empty vector and showed that ARFGAP3 overexpression promoted cell proliferation andmigration compared with control cells. We found that ARFGAP3 interacted with paxillin, a focal adhesion adaptor protein thatis important for cell mobility and migration. Small interfering RNA (siRNA)-mediated knockdown of ARFGAP3 showed thatARFGAP3 siRNA markedly reduced LNCaP cell growth. Androgen receptor (AR)-dependent transactivation activity on prostatespecificantigen (PSA) enhancer was synergistically promoted by exogenous ARFGAP3 and paxillin expression, as shown byluciferase assay in LNCaP cells. Thus, our results suggest that ARFGAP3 is a novel androgen-regulated gene that can promoteprostate cancer cell proliferation and migration in collaboration with paxillin.


Sign in / Sign up

Export Citation Format

Share Document