- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Bone Tissue Engineering Materials
- Cell Adhesion Molecules Research
- Nuclear Structure and Function
- Force Microscopy Techniques and Applications
- Microfluidic and Bio-sensing Technologies
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Collagen: Extraction and Characterization
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Caveolin-1 and cellular processes
- Brake Systems and Friction Analysis
- Microtubule and mitosis dynamics
- Calcium Carbonate Crystallization and Inhibition
- Heat shock proteins research
- Graphene and Nanomaterials Applications
- Rheology and Fluid Dynamics Studies
- Photochromic and Fluorescence Chemistry
- Connective tissue disorders research
- Blood properties and coagulation
- Axon Guidance and Neuronal Signaling
- Ultrasound and Hyperthermia Applications
- Bone health and treatments
University of Glasgow
2018-2025
Wellcome Centre for Cell-Matrix Research
2018-2022
Manchester Academic Health Science Centre
2018-2022
University of Manchester
2018-2022
Glasgow Life
2021
GeoEcoMar
2021
Imperial College London
2015
Highlights•Fast-moving cells in 3D matrix establish low membrane tension at the rear•Caveolae form response to and recruit GEF Ect2•Ect2 activates RhoA promote F-actin organization rear retraction•Positive feedback between contractility reinforces retractionSummaryIn development, wound healing, cancer metastasis, vertebrate move through interstitial matrix, responding chemical physical guidance cues. Protrusion cell front has been extensively studied, but retraction phase of migration cycle...
As cell function and phenotype can be directed by the mechanical characteristics of surrounding matrix, hydrogels have become important platforms for culture systems, with properties that tuned external stimuli, such as divalent cations, enzymatic treatment, pH. However, many these stimuli directly affect behavior, making it difficult to distinguish purely signaling events. This study reports on development a hydrogel incorporates photoswitchable cross-linkers, which reversibly alter their...
Studies of cellular mechano-signaling have often utilized static models that do not fully replicate the dynamics living tissues. Here, we examine time-dependent response primary human mesenchymal stem cells (hMSCs) to cyclic tensile strain (CTS). At low-intensity (1 h, 4% CTS at 1 Hz), cell characteristics mimic responses increased substrate stiffness. As regime is intensified (frequency 5 characterize rapid establishment a broad, structured and reversible protein-level response, even as...
The mechanical environment can influence cell behaviour, including changes to transcriptional and proteomic regulation, morphology and, in the case of stem cells, commitment lineage. However, current tools for characterizing substrates' properties, such as atomic force microscopy (AFM), often do not fully recapitulate length time scales over which cells 'feel' substrates. Here, we show that an immortalised, clonal line human mesenchymal (MSCs) maintains responsiveness substrate mechanics...
Abstract Laminins (LMs) are important structural proteins of the extracellular matrix (ECM). The abundance every LM isoform is tissue‐dependent, suggesting that has tissue‐specific roles. binds growth factors (GFs), which powerful cytokines widely used in tissue engineering due to their ability control stem cell differentiation. Currently, most commonly ECM mimetic material vitro Matrigel, a undefined composition containing and various GFs, but subjected batch variability lacking...
It is established that the mechanical properties of hydrogels control fate (stem) cells. However, despite its importance, a one-to-one correspondence between gels' stiffness and cell behaviour still missing from literature. In this work, viscoelastic Poly(ethylene-glycol) (PEG)-based - broadly used in 3D cultures whose can be tuned to resemble those different biological tissues are investigated by means rheological measurements performed at length scales. When compared with literature...
<title>Abstract</title> Mechanosensitive ion channels, such as Piezo1, have emerged having fundamental roles in sensing the mechanical properties of extracellular matrix (ECM). However, whether and how Piezo1 senses time-dependent ECM properties, that is viscoelasticity, remains unknown. To address this question, we combined an immortalised mesenchymal stem cell (MSC) line which expression can be silenced with soft stiff viscoelastic hydrogels independently tuneable elastic viscous moduli....
Living biointerfaces are a new class of biomaterials combining living cells and polymeric matrices that can act as biologically active instructive materials host provide signals to surrounding cells. Here, based on Lactococcus lactis control hematopoietic stem in 2D surfaces 3D hydrogels introduced. L. is modified express C-X-C motif chemokine ligand 12 (CXCL12), thrombopoietin (TPO), vascular cell adhesion protein 1 (VCAM1), the 7th-10th type III domains human plasma fibronectin (FN
This research is aimed at understanding the mechanisms that give rise to friction induced noise in automotive windscreen wipers, with a focus on frequencies between 500 and 3500 Hz. To study this phenomenon, experimental friction, sound, high-speed video measurements are combined finite element modeling of rubber wiper/glass contact. In agreement previous research, simultaneous sound showed wiper frequency range results from negative damping effect caused by dependence speed mixed...
In this work, Engineered Living Materials (ELMs), based on the combination of genetically-modified bacteria and mineral-reinforced organic matrices, endowed with self-healing or regenerative properties adaptation to specific biological environments were developed. Concretely, we produced ELMs combining human mesenchymal stem cells (hMSCs) Lactococcus lactis (L. lactis), which was specifically programmed deliver bone morphogenetic protein (BMP-2) upon external stimulation using nisin, into...
Abstract Living interfaces are established as a novel class of active materials that aim to provide an alternative traditional static cell culture methods by enabling users accurately control behaviour in precise, dynamic, and reliable system‐internal manner. To this day, the only reported biointerface has been coculture between biofilm nonpathogenic genetically engineered bacteria mammalian cells, where recombinant proteins produced directly influence behaviour. In work, is presented...
The tumor microenvironment plays an important role in cancer development and the use of 3D vitro systems that decouple different elements this is critical for study progression. In neuroblastoma (NB), vitronectin (VN), extracellular matrix protein, has been linked to poor prognosis appears as a promising therapeutic target. Here, we developed hydrogels incorporate VN into polyethylene glycol (PEG) hydrogel networks recapitulate native NB microenvironment. stiffness VN/PEG was modulated be...
Brushite cements are promising bone regeneration materials with limited biological and mechanical properties. Here, we engineer a mechanically improved brushite–collagen type I cement enhanced properties by use of chiral chemistry; d- l-tartaric acid were used to limit crystal growth increase the cements. The impact molecules on was examined Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM). A 3-point bend test utilized study fracture...
Summary Our current understanding of cellular mechano-signalling is based on static models, which do not replicate the dynamics living tissues. Here, we examined time-dependent response primary human mesenchymal stem cells (hMSCs) to cyclic tensile strain (CTS). At low-intensity (1 hour, 4% CTS at 1 Hz) morphological changes mimicked responses increased substrate stiffness. As regime was intensified (frequency 5 Hz), characterised rapid establishment a broad, structured and reversible...
Cell function can be directly influenced by the mechanical and structural properties of extracellular environment. In particular, cell morphology phenotype regulated via modulation both stiffness surface topography culture substrates. Previous studies have highlighted ability to design substrates optimise function. Many such examples, however, employ photo-crosslinkable polymers with a terminal or profile. This study presents system polyacrylamide hydrogels, where tailored matrix altered in...
Collagen type I lacks affinity for growth factors (GFs) and yet it is clinically used to deliver bone morphogenic protein 2 (BMP-2), a potent osteogenic factor. To mitigate this lack of affinity, supra-physiological concentrations BMP-2 are loaded in collagen sponges leading uncontrolled leakage out the material. This has led important adverse side effects such as carcinogenesis. Here, we design recombinant dual fragments, produced E. Coli, which contain two regions, one that spontaneously...
Abstract The mechanical environment can influence cell behaviour, including changes to transcriptional and proteomic regulation, morphology and, in the case of stem cells, commitment lineage. However, current tools for characterizing substrates’ properties, such as atomic force microscopy (AFM), often do not fully recapitulate length time scales over which cells ‘feel’ substrates. Here, we show that an immortalised, clonal line human mesenchymal (MSCs) maintained responsiveness substrate...
In article number 2010225, Manuel Salmeron-Sanchez and co-workers develop hydrogels that incorporate specific laminin isoforms. Laminins are ECM molecules tissue specific, promote integrin binding, sequester growth factors. The versatility of the system to engineer in vitro 3D cultures controlled stiffness mesenchymal stem cell differentiation (using LM 521) or neural 411) is demonstrated.
Abstract Mechanosensitive ion channels have emerged as fundamental proteins in sensing extracellular matrix (ECM) mechanics. Among those, Piezo1 has been proposed a key mechanosensor cells. However, whether and how senses time-dependent ECM mechanical properties (i.e., viscoelasticity) remains unknown. To address this question, we combined an immortalised mesenchymal stem cell (MSC) line with adjustable expression soft (400 Pa) stiff (25 kPa) viscoelastic hydrogels independently tuneable...
In development, wound healing and cancer metastasis vertebrate cells move through 3D interstitial matrix, responding to chemical physical guidance cues. Protrusion at the cell front has been extensively studied, but retraction phase of migration cycle is not well understood. Here we show that fast moving guided by matrix cues establish positive feedback control rear sensing membrane tension. We reveal a mechanism in durotaxis controlled caveolae, which form response low tension rear....
The ability to create cell-laden fluidic models that mimic the geometries and physical properties of vascularized tissue would be extremely beneficial study disease etiologies future therapies, including in case cancer where there is increasing interest studying alterations microvasculature. Engineered systems can present significant advantages over animal studies, alleviating challenges associated with variable complexity control. Three-dimensional (3D)-printable tissue-mimicking hydrogels...