Viscoelastic properties of ECM differentially regulate monocyte patterns of gene expression
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PROVIDER: PRJNA852161 | ENA |
REPOSITORIES: ENA
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2022-07-11 | GSE206769 | GEO
Project description:Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function compared to those on purely elastic surfaces. Slow-relaxing viscoelastic substrates reduce lamin A/C expression and enhance nuclear remodeling. These structural changes are accompanied by a global increase in euchromatin marks and local increase in chromatin accessibility at cis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic substrates improve the reprogramming efficiency from fibroblasts into neurons and induced pluripotent stem cells. Collectively, our findings unravel the roles of matrix viscoelasticity in epigenetic regulation and cell reprogramming, with implications for designing smart materials for cell fate engineering.
2025-04-02 | GSE293383 | GEO
Project description:Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function compared to those on purely elastic surfaces. Slow-relaxing viscoelastic substrates reduce lamin A/C expression and enhance nuclear remodeling. These structural changes are accompanied by a global increase in euchromatin marks and local increase in chromatin accessibility at cis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic substrates improve the reprogramming efficiency from fibroblasts into neurons and induced pluripotent stem cells. Collectively, our findings unravel the roles of matrix viscoelasticity in epigenetic regulation and cell reprogramming, with implications for designing smart materials for cell fate engineering.
2025-04-02 | GSE293382 | GEO
Project description:This study presents a comprehensive characterization of the viscoelastic and structural properties of Bovine Submaxillary Mucin (BSM), a good biomaterial model system for mucins and mucus in general. We conducted concentration studies of BSM and examined the effects of various additives - sodium chloride, calcium chloride, lysozyme, and DNA - on its rheological behavior. Through oscillatory and shear flow macrorheological experiments, we established a detailed correlation between the concentration of BSM and its viscoelastic properties, uncovering changes in the rheological moduli with the addition of sodium and calcium chloride, particularly at higher concentrations. This highlights the mucins responsiveness to ionic strength and composition variations. The presence of lysozyme and DNA further influenced the rheological characteristics of BSM, adding a new dimension to our understanding of mucin behavior. The rheological spectra could be well-described by a Fractional Kelvin-Voigt Model (FKVM), which allows to describe the complete behavior with a minimum of model parameters. A detailed proteomics analysis provided insight into the molecular interactions within BSM, enhancing our understanding of its structural intricacies. Complementing this, cryo-scanning electron microscopy (cryo-SEM) was employed to visualize the microstructural alterations and network properties in relation to the rheological data. By elucidating the complex interplay between mucin concentration, environmental conditions, and viscoelastic properties, this research significantly contributes to the field of mucus research and lays an important basis for future studies and advanced applications of numerous mucin-based biomaterials.
2024-07-25 | PXD048381 | Pride
Project description:The material properties of tissues and their mechanical state is an important factor in development, disease, regenerative medicine and tissue engineering. Here we describe a microrheological measurement technique utilizing aggregates of microinjected ferromagnetic nickel particles to probe the viscoelastic properties of embryonic tissues. Quail embryos were cultured in a plastic incubator chamber located at the center of two pairs of crossed electromagnets. We found a pronounced viscoelastic behavior within the ECM-rich region separating the mesoderm and endoderm in Hamburger Hamilton stage 10 quail embryos, consistent with a Zener (standard generalized solid) model. The viscoelastic response is about 45% of the total response, with a characteristic relaxation time of 1.3 s.
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Project description:Rationale: We recently demonstrated that the triple combination CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves lung ventilation and airway mucus plugging determined by multiple-breath washout and magnetic resonance imaging in CF patients with at least one F508del allele. However, effects of ELX/TEZ/IVA on viscoelastic properties of airway mucus, chronic airway infection and inflammation have not been studied. Objectives: To examine the effects of ELX/TEZ/IVA on airway mucus rheology, microbiome and inflammation in CF patients with one or two F508del alleles aged 12 years and older. Methods: In this prospective observational study, we determined sputum rheology, microbiome, inflammation markers and proteome before and 1, 3 and 12 months after initiation of ELX/TEZ/IVA. Measurements and Main Results: CF patients with at least one F508del allele and healthy controls were enrolled in this study. ELX/TEZ/IVA improved the elastic and viscous modulus of CF sputum. Further, ELX/TEZ/IVA improved the microbiome α-diversity and decreased the relative abundance of Pseudomonas aeruginosa (P<0.05) in CF sputum. ELX/TEZ/IVA also reduced IL-8 and free NE activity, and shifted the CF sputum proteome towards healthy. Conclusions: Our data demonstrate that ELX/TEZ/IVA improves sputum viscoelastic properties, chronic airway infection and inflammation in CF patients with at least one F508del allele, however, without reaching levels close to healthy.
2023-06-22 | PXD041844 | Pride
Project description:Immunotherapy shows promise in cancer treatment, but its effectiveness and durability remain limited, and improved technology for engineering immune cells is necessary. Here we develop a scalable platform that creates synthetic viscoelastic activating cells (SynVACs) with programmable mechanical and chemical properties. We demonstrate that the viscoelastic nature of SynVACs significantly impacts T cell functionality. Compared to rigid or elastic microspheres, SynVACs greatly enhance human T cell expansion, achieving approximately 90% chimeric antigen receptor (CAR) transduction efficiency. Additionally, SynVACs promote CD8+ T cell generation while suppressing regulatory T cell formation, resulting in enhanced tumor killing capability. Notably, expanding CAR-T cells with SynVACs leads to a ten-fold increase in T memory stem cells (TMSCs). These engineered CAR-T cells exhibit superior efficacy in eliminating tumor cells in a human lymphoma and ovarian xenograft mouse model, persisting in vivo for longer time period. These findings underscore the crucial role of mechanical signals in T cell engineering and highlight SynVACs' potential in CAR-T therapy and imunoengineering applications.
2023-09-12 | GSE242531 | GEO
Project description:hsa-miRNA-548v controls the viscoelastic properties of human cardiomyocytes and improves their relaxation rates
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Project description:The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver’s metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver’s metabolic function in vivo. Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron-emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR), and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography–mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into ‘stiff’ and ‘soft’ subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange.In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients.
2022-12-21 | PXD036659 | Pride
Project description:The impairment of left ventricular (LV) diastolic function with inadequate increase in myocardial relaxation velocity directly results in lower LV compliance, increased LV filling pressures and heart failure symptoms. The development of agents facilitating the relaxation of human cardiomyocytes requires a better understanding of the underlying regulatory mechanisms. We performed a high-content microscopy-based screening in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using a library of 2565 human miRNA mimics and measured relaxation kinetics via high-computing analyses of motion movies. We identified hsa-miR-548v, a primate specific miRNA, as the miRNA producing the largest increase in relaxation velocities. This positive lusitropic effect was reproduced in engineered cardiac tissues generated with healthy and BRAF T599R mutant hiPSC-CMs, and was independent of changes in calcium transients. Consistent with improvements in viscoelastic responses to mechanical stretch, RNA-sequencing showed that hsa-miR-548v down-regulated multiple targets, especially components of the mechano-sensing machinery. The exogenous administration of hsa-miR-548v in hiPSC-CMs notably resulted in a significant reduction of ANKRD1/CARP1 expression and localization at the sarcomeric I-band. This study suggests that the sarcomere I-band is a critical control center of the ability of cardiomyocytes to relax and a target for improving relaxation and diastolic dysfunction.
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