A5078074638- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Quantum and electron transport phenomena
- Chemotherapy-induced cardiotoxicity and mitigation
- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Cardiovascular Effects of Exercise
- Surface and Thin Film Phenomena
- Potassium and Related Disorders
- Electron Spin Resonance Studies
- Microfluidic and Bio-sensing Technologies
- Ion Transport and Channel Regulation
- Force Microscopy Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Photochemistry and Electron Transfer Studies
- Orbital Angular Momentum in Optics
- Semiconductor materials and devices
- Advanced Fluorescence Microscopy Techniques
- Fuel Cells and Related Materials
- Elasticity and Material Modeling
- Physics of Superconductivity and Magnetism
- Molecular Junctions and Nanostructures
- Optical Imaging and Spectroscopy Techniques
Imperial College London
2023-2024
King's College London
2008-2023
St Thomas' Hospital
2018-2019
London Centre for Nanotechnology
2013-2014
University College London
2013-2014
King's College - North Carolina
2008
Monash University
2006
Cavendish Hospital
2002-2004
University of Cambridge
2002
The cell cortex is a thin network of actin, myosin motors, and associated proteins that underlies the plasma membrane in most eukaryotic cells. It enables cells to resist extracellular stresses, perform mechanical work, change shape. Cortical structural properties depend strongly on relative turnover rates its constituents, but quantitative data these remain elusive. Using photobleaching experiments, we analyzed dynamics three classes within living cells: scaffold protein (actin),...
While the molecular and biophysical mechanisms underlying cell protrusion on two-dimensional substrates are well understood, our knowledge of actin structures driving in three-dimensional environments is poor, despite relevance to inflammation, development cancer. Here we report that, during chemotactic migration through microchannels with 5 μm × cross-sections, HL60 neutrophil-like cells assemble an actin-rich slab filling whole channel cross-section at their front. This leading edge...
Cardiac contraction is the result of integrated cellular, tissue and organ function. Biophysical in silico cardiac models offer a systematic approach for studying these multi-scale interactions. The computational cost such high, due to their multi-parametric nonlinear nature. This has so far made it difficult perform model fitting prevented global sensitivity analysis (GSA) studies. We propose machine learning based on Gaussian process emulation simulations using probabilistic surrogate...
Hypokalemia occurs in up to 20% of hospitalized patients and is associated with increased incidence ventricular atrial fibrillation. It unclear whether these differing types arrhythmia result from direct perhaps distinct effects hypokalemia on cardiomyocytes.To investigate proarrhythmic mechanisms myocytes.Experiments were performed isolated rat myocytes exposed simulated conditions (reduction extracellular [K+] 5.0 2.7 mmol/L) supported by mathematical modeling studies. Ventricular cells...
Abstract Uncovering cellular responses from heterogeneous genomic data is crucial for molecular medicine in particular drug safety. This can be realized by integrating the activities networks of interacting proteins. As proof-of-concept we challenge network modeling with time-resolved proteome, transcriptome and methylome measurements iPSC-derived human 3D cardiac microtissues to elucidate adverse mechanisms anthracycline cardiotoxicity measured four different drugs (doxorubicin, epirubicin,...
Key points Hypokalaemia is a risk factor for development of ventricular arrhythmias. In rat myocytes, low extracellular K + (corresponding to clinical moderate hypokalaemia) increased Ca 2+ wave probability, transient amplitude, sarcoplasmic reticulum (SR) load and induced SR leak. Low reduced Na ,K ‐ATPase (NKA) activity hyperpolarized the resting membrane potential in myocytes. Both experimental data modelling indicate that NKA subsequent accumulation sensed by , exchanger (NCX) lead...
The integration of protein function studied in vitro a dynamic system like the cell lamellipodium remains significant challenge. One reason is apparent contradictory effect that perturbations some proteins can have on overall dynamics, depending exact conditions. Theoretical modelling offers one approach for understanding balance between mechanisms drive and regulate actin network growth decay. Most models use 'bottom-up' approach, involving explicitly assembling biochemical components to...
The length-dependent activation (LDA) of maximum force and calcium sensitivity are established features cardiac muscle contraction but the dominant underlying mechanisms remain to be fully clarified. Alongside well-documented regulation via thin filaments, experiments have identified an additional force-dependent thick-filament activation, whereby myosin heads parked in a so-called off state become available generate force. This process produces feedback effect that may potentially drive...
The Na(+)/K(+) ATPase (NKA) plays a critical role in maintaining ionic homeostasis and dynamic function cardiac myocytes, within both the vivo cell silico models. Physiological conditions differ significantly between mammalian species. However, most existing formulations of NKA used to simulate computational models are derived from broad range experimental sources spanning many animal resultant inability these discern species-specific features is significant obstacle achieving detailed...
The effect of substrate bias and surface gate voltage on the low temperature resistivity a Si-MOSFET is studied for electron concentrations where increases with increasing temperature. This technique offers two degrees freedom controlling concentration device mobility, thereby providing means to evaluate relative importance electron-electron interactions disorder in this so-called ``metallic'' regime. For temperatures well below Fermi temperature, data obey scaling law parameter...
Myosin generates force by a rotation of its lever arm. Crystal structures myosin II indicate an unloaded working stroke 10–12 nm, range confirmed recent x-ray interference experiments. However, when actin filament, held between two weakly, optically trapped beads is made to interact with single head skeletal myosin, the bead displacements have often been reported as having mean value 5–6 that commonly interpreted stroke. In general, observed displacement not expected be equal because...
Abstract The data currently described was generated within the EU/FP7 HeCaToS project ( He patic and Ca rdiac To xicity S ystems modeling). aimed to develop an in silico prediction system contribute drug safety assessment for humans. For this purpose, multi-omics of repeated dose toxicity were obtained 10 hepatotoxic cardiotoxic compounds. Most gained from vitro experiments which 3D microtissues (either hepatic or cardiac) exposed a therapeutic (physiologically relevant concentrations...
Cardiac mechanics models are developed to represent a high level of detail, including refined anatomies, accurate cell models, and platforms link microscale physiology whole-organ function. However, cardiac biomechanics still have limited clinical translation. In this review, we provide picture focusing on their We review the main experimental data used in as well steps followed literature generate anatomical meshes ready for simulations. describe active passive different lumped parameter...
Late-onset heart failure (HF) is a known side effect of doxorubicin chemotherapy. Typically, patients are diagnosed when already at an irreversible stage HF, which allows few or no treatment options. Identifying the causes compromised cardiac function in this patient group may improve early diagnosis and support selection. To link doxorubicin-induced changes cellular tissue mechanical properties to overall function, we apply multiscale biophysical biomechanics model measure plausibility...
The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, intracellular levels order to maintain function. However, on longer time scales following onset of ventricular pressure overload, such may begin inhibit function ultimately lead heart failure. This progression from compensatory decompensatory behavior is poorly understood, particular owing absence unified perspective concomitantly subsystems. To...
The rise and saturation, in a parallel magnetic field ${B}_{\ensuremath{\Vert}},$ of the resistivity two-dimensional electron systems on metallic side apparent metal-insulator transition (MIT) can be interpreted as destruction state. It is also compatible, however, with reduction screening charged impurities, resulting from breaking spin degeneracy, traditional Fermi liquid. We demonstrate, using Si-MOSFET, that electrons strong ${B}_{\ensuremath{\Vert}}$ to Si-${\mathrm{SiO}}_{2}$ interface...
The elastic properties of the cell membrane play a crucial role in determining equilibrium shape cell, as well its response to external forces it experiences physiological environment. Red blood cells are favored system for studying because their simple structure: lipid bilayer coupled cytoskeleton and no cytoplasmic cytoskeleton. An optical trap is used stretch red fixed glass surface, along symmetry axis by pulling on micron-sized latex bead that bound at center exposed dimple. system,...
Doxorubicin, a potent anticancer drug, has well known dose‐dependent cardiotoxic side effects. In particular, doxorubicin exposure disrupts protein expression and impacts multiple biochemical pathways through the generation of reactive oxide species oxidative stress, which in turn leads to cardiomyopathy congestive heart failure. Specific effects at biochemical, cellular, tissue levels, have been extensively studied. However, systematic quantitative assessment relative significance these on...