A5090094757- Cellular Mechanics and Interactions
- Liver physiology and pathology
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Microtubule and mitosis dynamics
- Erythrocyte Function and Pathophysiology
- 3D Printing in Biomedical Research
- Hippo pathway signaling and YAP/TAZ
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Retinoids in leukemia and cellular processes
- Caveolin-1 and cellular processes
- Glycosylation and Glycoproteins Research
- Axon Guidance and Neuronal Signaling
- Supramolecular Self-Assembly in Materials
- Wnt/β-catenin signaling in development and cancer
- Magnetic and Electromagnetic Effects
- Chemical Synthesis and Analysis
- Zebrafish Biomedical Research Applications
- Elasticity and Material Modeling
- Advanced biosensing and bioanalysis techniques
- Cellular transport and secretion
- Advanced Fluorescence Microscopy Techniques
- Monoclonal and Polyclonal Antibodies Research
- Force Microscopy Techniques and Applications
Universidad Carlos III de Madrid
2024
Imperial College London
2016-2024
Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic one of stiffest all human solid carcinomas characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered recapitulate pancreatic cancer, several lines as model investigate effect stiffness in epithelial-mesenchymal transition (EMT) resistance chemotherapeutics. We...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite vitamin A, restores mechanical quiescence in PSCs via mechanism involving retinoic acid receptor beta (RAR-β)-dependent downregulation actomyosin (MLC-2) contractility. We show ATRA...
This work introduces NeoMag, a system designed to enhance cell mechanics assays in substrate deformation studies. NeoMag uses multidomain magneto-active materials mechanically actuate the substrate, transmitting reversible mechanical cues cells. The boasts full flexibility alternating loading modes, seamlessly adapting both upright and inverted microscopes. substrates facilitate mechanobiology on 2D 3D cultures. integration of with nanoindenters allows for precise evaluation cellular...
Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates fundamental processes cells such as growth, survival, migration. FAK one of the first molecules recruited to response external mechanical stimuli therefore pivotal mediator cell mechanosignaling, relays these other mechanotransducers within cytoplasm. Yes-associated protein (YAP) has been identified recently core mechanotransducers. YAP translocates nucleus following changes mechanics promote expression genes...
Abstract Liver fibrosis is characterised by a dense and highly cross-linked extracellular matrix (ECM) which promotes progression of diseases such as hepatocellular carcinoma. The fibrotic microenvironment an increased stiffness, with rigidity associated disease progression. External stiffness known to promote hepatic stellate cell (HSC) activation through mechanotransduction, leading secretion ECM components. HSCs are key effector cells maintain the composition in health disease, not only...
Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive malignancy characterised by the presence of extensive desmoplasia, thought to be responsible for poor response patients systemic therapies. stellate cells (PSCs) are key mediators in production this fibrotic stroma, upon activation transitioning a myofibroblast-like, high matrix secreting phenotype. Given their importance disease progression, characterisation PSC has been extensive, however one aspect that overlooked mechano-sensing...
Liver fibrosis, a condition characterized by extensive deposition and cross-linking of extracellular matrix (ECM) proteins, is idiosyncratic in cases chronic liver injury. The dysregulation ECM remodeling hepatic stellate cells (HSCs), the main mediators results an elevated stiffness that drives development disease such as cirrhosis hepatocellular carcinoma. Tissue inhibitor metalloproteinase-1 (TIMP-1) key element regulation remodeling, which modulates degradation turnover components. We...
The mechanical unfolding of proteins is a cellular mechanism for force transduction with potentially broad implications in cell fate. Despite this, the by which protein elicits differential downstream signalling pathways remains poorly understood. Here, we used engineering, atomic microscopy, and biophysical tools to delineate how controls mechanics. Deleted liver cancer 1 (DLC1) negative regulator Ras homolog family member A (RhoA) contractility that regulates behaviour when localised focal...
Article12 December 2018Open Access Transparent process Tamoxifen mechanically reprograms the tumor microenvironment via HIF-1A and reduces cancer cell survival Ernesto Cortes Cellular Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, UK Search for more papers by this author Dariusz Lachowski orcid.org/0000-0003-1194-8019 Benjamin Robinson Muge Sarper Jaakko S Teppo orcid.org/0000-0003-1022-5572 Institute Biotechnology, University Helsinki, Finland...
Scientific Report11 December 2018Open Access Transparent process GPER is a mechanoregulator of pancreatic stellate cells and the tumor microenvironment Ernesto Cortes Cellular Molecular Biomechanics Laboratory, Department Bioengineering, Imperial College London, UK Search for more papers by this author Muge Sarper Benjamin Robinson Dariusz Lachowski orcid.org/0000-0003-1194-8019 Antonios Chronopoulos Stephen D Thorpe Corresponding Author [email protected] Institute School Engineering...
Hepatic stellate cells (HSCs) are essential perisinusoidal in both healthy and diseased liver. HSCs modulate extracellular matrix (ECM) homeostasis when quiescent, but liver fibrosis, become activated promote excess deposition of ECM molecules tissue stiffening via force generation mechanosensing. In hepatocellular carcinoma (HCC), infiltrate the stroma migrate to tumor core facilitate paracrine signaling with cancer cells. Because function is known be modulated by retinoids, we investigated...
Tamoxifen has been used for many years to target estrogen receptor signalling in breast cancer cells. is also an agonist of the G protein-coupled (GPER), a GPCR ubiquitously expressed tissues that mediates acute response estrogens. Here we report tamoxifen promotes mechanical quiescence hepatic stellate cells (HSCs), stromal fibroblast-like whose activation triggers and perpetuates liver fibrosis hepatocellular carcinomas. This deactivation mediated by GPER/RhoA/myosin axis induces YAP...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness high metastatic rate. Retinoids, compounds derived from vitamin A, have a history clinical use in cancer for their anti-proliferative differentiation effects, more recently been explored as anti-stromal therapies PDAC ability to induce mechanical quiescence associated fibroblasts. Here, we demonstrate that retinoic acid...
Mechanosensing is a ubiquitous process to translate external mechanical stimuli into biological responses. Piezo1 ion channels are directly gated by forces and play an essential role in cellular mechanotransduction. However, readouts of activity mainly examined invasive or indirect techniques, such as electrophysiological analyses cytosolic calcium imaging. Here, we introduce GenEPi, genetically-encoded fluorescent reporter for non-invasive optical monitoring Piezo1-dependent activity. We...
The invasive properties of cancer cells are intimately linked to their mechanical phenotype, which can be regulated by intracellular biochemical signalling. Cell contractility, induced mechanotransduction a stiff fibrotic matrix, and the epithelial–mesenchymal transition (EMT) promote invasion. Metastasis involves pushing through basement membrane into stroma—both altered in composition with progression. Agonists G protein-coupled oestrogen receptor (GPER), such as tamoxifen, have been...
Human pluripotent stem cell-derived hepatocytes (hPSC-Heps) may be suitable for treating liver diseases, but differentiation protocols often fail to yield adult-like cells. We hypothesised that replicating healthy niche biochemical and biophysical cues would produce with desired metabolic functionality. Using 2D synthetic hydrogels which independently control mechanical properties cues, we found culturing hPSC-Heps on surfaces matching the stiffness of fibrotic tissue upregulated expression...
The tumor microenvironment plays a critical role in modulating cancer cell migration, metabolism, and malignancy, thus, highlighting the need to develop vitro culture systems that can recapitulate its abnormal properties. While variety of stiffness-tunable biomaterials, reviewed here, have been developed mimic rigidity extracellular matrix, broader context (including pH temperature) remain comparably unexplored, partially due difficulty independently tuning these parameters. Here, we...
Mechanical forces regulate cell functions through multiple pathways. G protein-coupled estrogen receptor (GPER) is a seven transmembrane that ubiquitously expressed across tissues and mediates the acute cellular response to estrogens. Here, we demonstrate an unidentified role of GPER as mechanoregulator. signaling controls assembly stress fibers, dynamics associated focal adhesions, polarization via RhoA. activation inhibits F-actin polymerization, subsequently triggers negative feedback...
Mechanical and Functional Responses in Astrocytes respond to mechanical actuation changing their structure, properties functional activity. A magneto-mechanical system simulates traumatic brain injury stroke-induced substrate deformations vitro. These time-evolving lead intertwined remodeling of actin cytoskeleton modulating the cell activating Piezo1. coordinated changes may influence protective role astrocytes for neighboring neurons. More details can be found article number 2312497 by...