Labernadie A.,Institute for Bioengineering of Catalonia |
Kato T.,Francis Crick Institute |
Brugues A.,Institute for Bioengineering of Catalonia |
Serra-Picamal X.,Institute for Bioengineering of Catalonia |
And 15 more authors.
Nature Cell Biology | Year: 2017
Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.
Izquierdo-Serra M.,Institute Of Bioenginyeria Of Catalonia |
Gascon-Moya M.,Autonomous University of Barcelona |
Hirtz J.J.,Columbia University |
Pittolo S.,Institute Of Bioenginyeria Of Catalonia |
And 10 more authors.
Journal of the American Chemical Society | Year: 2014
Synthetic photochromic compounds can be designed to control a variety of proteins and their biochemical functions in living cells, but the high spatiotemporal precision and tissue penetration of two-photon stimulation have never been investigated in these molecules. Here we demonstrate two-photon excitation of azobenzene-based protein switches and versatile strategies to enhance their photochemical responses. This enables new applications to control the activation of neurons and astrocytes with cellular and subcellular resolution. © 2014 American Chemical Society.
Pena E.,Aragon Institute of Engineering Research |
Pena E.,Research Center Biomedica en Red en Bioingenieria
Mechanics Research Communications | Year: 2011
Several typical equations for damage variables are proposed in the literature in the context of Continuum Damage Mechanics for fibred materials such as soft biological tissues. All these proposed functions are defined for the same or similar soft tissues. The applicability of some of them, however, is not clear. The paper compares a series of damage functions given in the literature for the description of softening in soft biological tissues. In addition, a new damage function is introduced. The difference in the response of this function compared to those previously proposed in the literature is that the first derivative is zero at the initial damage state. This represents a potential advantage with respect to numerical calculations since smooth derivatives are obtained. © 2011 Elsevier Ltd. All rights reserved.
Prieto-Simon B.,Institute for Bioengineering of Catalonia IBEC |
Prieto-Simon B.,Research Center Biomedica en Red en Bioingenieria |
Prieto-Simon B.,University of South Australia |
Samitier J.,Institute for Bioengineering of Catalonia IBEC |
And 2 more authors.
Analytical Chemistry | Year: 2014
A novel sensing strategy for electrochemical aptamer-based sensors is presented. Nucleic acid aptamers are considered alternatives to antibodies. However, some of their intrinsic properties, such as that they can undergo conformational changes during the binding of the target, can be used to design novel sensing strategies. Unlike other electrochemical "signal off" aptamer-based sensors, we report a strategy based on enzymatic inhibition. Our approach shows the feasibility to detect small molecules based on the aptamer conformational change induced by the target that leads to the inhibition of the enzyme used as a label. Additionally, we prove the ability to regenerate the function of the aptasensor by simply applying a short potential pulse. As a proof-of-concept, the widely used aptamer for ochratoxin A (OTA) has been selected as a model. After self-assembling short oligonucleotides onto a gold electrode, complementary to the 3′ end of the aptamer, hybridization of the aptamer takes place. To investigate the mechanism induced by the OTA-binding, surface plasmon resonance assays were performed, which confirmed the conformational switch of the aptamer rather than the aptamer displacement by dehybridization from the DNA-modified sensor surface. The electrochemical sensor can successfully detect OTA in wine at the limits stipulated by the European Commission. Given its sensitivity, rapid and easy detection, and regeneration, it can be envisaged as screening tool for OTA detection. Moreover, this sensing strategy has the potential to be applied to other aptamer-based biochemical assays for the detection of small molecules in the fields of food safety, environmental monitoring, and medical diagnostics. © 2013 American Chemical Society.
Cilla M.,Aragon Institute of Engineering Research |
Cilla M.,Research Center Biomedica en Red en Bioingenieria |
Martinez J.,Centro Universitario Of La Defensa |
Pena E.,Aragon Institute of Engineering Research |
And 3 more authors.
IEEE Transactions on Biomedical Engineering | Year: 2012
Atherosclerotic cardiovascular disease results in millions of sudden deaths annually, and coronary artery disease accounts for the majority of this toll. Plaque rupture plays main role in the majority of acute coronary syndromes. Rupture has been usually associated with stress concentrations, which are determined mainly by tissue properties and plaque geometry. The aim of this study is develop a tool, using machine learning techniques to assist the clinical professionals on decisions of the vulnerability of the atheroma plaque. In practice, the main drawbacks of 3-D finite element analysis to predict the vulnerability risk are the huge main memories required and the long computation times. Therefore, it is essential to use these methods which are faster and more efficient. This paper discusses two potential applications of computational technologies, artificial neural networks and support vector machines, used to assess the role of maximum principal stress in a coronary vessel with atheroma plaque as a function of the main geometrical features in order to quantify the vulnerability risk. © 2006 IEEE.
Lopez-Miguel A.,University of Valladolid |
Lopez-Miguel A.,Vision ID SL |
Teson M.,University of Valladolid |
Martin-Montanez V.,University of Valladolid |
And 8 more authors.
American Journal of Ophthalmology | Year: 2014
Purpose To determine if controlled environmental conditions can induce acute exacerbations of signs and symptoms in dry eye and asymptomatic subjects. Design Prospective cross-sectional study. Methods Nineteen patients with dry eye and 20 asymptomatic controls were exposed to controlled low humidity (5% relative humidity, desiccating environment) for 2 hours in our Controlled Environmental Research Laboratory at the University of Valladolid. The patients completed the Single-Item Score Dry Eye Questionnaire and the following diagnostic tests were performed before and after exposure: tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear film break-up time, Schirmer test, and ocular surface vital staining. Sixteen molecules in the tears samples were analyzed by multiplex bead analysis. Results After exposure, the patients and controls had a significant (P ≤.003) increase in corneal staining (from 0.68 ± 0.15 to 1.16 ± 0.14 and from 0.50 ± 0.15 to 1.30 ± 0.19, respectively), significantly decreased (P ≤.01) fluorescein tear film break-up time values (from 2.78 ± 0.56 seconds to 1.94 ± 0.24 seconds and from 2.81 ± 0.24 seconds to 2.13 ± 0.19 seconds, respectively), and significantly increased (P ≤.03) matrix metalproteinase 9 tear levels (from 10 054.4 ± 7326.6 pg/mL to 25 744.5 ± 13 212.4 pg/mL and from 10 620.5 ± 4494.3 pg/mL to 16 398.7 ± 5538.3 pg/mL, respectively). In the control group, the epidermal growth factor tear levels decreased significantly (P =.007; from 1872.1 ± 340.7 pg/mL to 1107.1 ± 173.6 pg/mL), and interleukin 6 levels increased significantly (P <.001; from 29.6 ± 5.8 pg/mL to 54.3 ± 8.3 pg/mL) after exposure. Conclusions Adult patients with mild-to-moderate dry eye and asymptomatic subjects of similar ages can experience acute exacerbation in an environmental chamber that resembles the sudden worsening that patients with dry eye experience daily. © 2014 BY ELSEVIER INC. ALL RIGHTS RESERVED.
Mousavi S.J.,Aragon Institute of Engineering Research |
Mousavi S.J.,University of Zaragoza |
Mousavi S.J.,Research Center Biomedica en Red en Bioingenieria |
Doblare M.,Aragon Institute of Engineering Research |
And 5 more authors.
Physical Biology | Year: 2014
Cell migration is a vital process in many biological phenomena ranging from wound healing to tissue regeneration. Over the past few years, it has been proven that in addition to cell-cell and cell-substrate mechanical interactions (mechanotaxis), cells can be driven by thermal, chemical and/or electrical stimuli. A numerical model was recently presented by the authors to analyse single cell migration in a multi-signalling substrate. That work is here extended to include multi-cell migration due to cell-cell interaction in a multi-signalling substrate under different conditions. This model is based on balancing the forces that act on the cell population in the presence of different guiding cues. Several numerical experiments are presented to illustrate the effect of different stimuli on the trajectory and final location of the cell population within a 3D heterogeneous multi-signalling substrate. Our findings indicate that although multi-cell migration is relatively similar to single cell migration in some aspects, the associated behaviour is very different. For instance, cell-cell interaction may delay single cell migration towards effective cues while increasing the magnitude of the average net cell traction force as well as the local velocity. Besides, the random movement of a cell within a cell population is slightly greater than that of single cell migration. Moreover, higher electrical field strength causes the cell slug to flatten near the cathode. On the other hand, as with single cell migration, the existence of electrotaxis dominates mechanotaxis, moving the cells to the cathode or anode pole located at the free surface. The numerical results here obtained are qualitatively consistent with related experimental works. © 2014 IOP Publishing Ltd.
Laguna P.,Aragon Institute of Engineering Research |
Laguna P.,Research Center Biomedica en Red en Bioingenieria |
Sornmo L.,Lund University
Journal of Electrocardiology | Year: 2014
The development of new techniques for detection and characterization of transient myocardial ischemia has benefited considerably from the STAFF III database, acquired in patients receiving elective prolonged percutaneous transluminal coronary angiography. The present article reviews a range of techniques developed and/or evaluated on the ECG signals of this database, including techniques for exploring abnormal intra-QRS potentials, QRS slopes, QRS angles, T wave morphology, T wave alternans, spatiotemporal ECG information, as well as heart rate dynamics. The detection of changes in body position is also briefly reviewed as it is intimately related to ischemia detection. © 2014 Elsevier Inc.
Rojas S.,Institute Dalta Tecnologia Parc Of Recerca Biomedica Of Barcelona |
Gispert J.D.,Institute Dalta Tecnologia Parc Of Recerca Biomedica Of Barcelona |
Gispert J.D.,Research Center Biomedica en Red en Bioingenieria |
Martin R.,Polytechnic University of Valencia |
And 8 more authors.
ACS Nano | Year: 2011
Nanoparticles have been proposed for several biomedical applications; however, in vivo biodistribution studies to confirm their potential are scarce. Nanodiamonds are carbon nanoparticles that have been recently proposed as a promising biomaterial. In this study, we labeled nanodiamonds with 18F to study their in vivo biodistribution by positron emission tomography. Moreover, the impact on the biodistribution of their kinetic particle size and of the surfactant agents has been evaluated. Radiolabeled diamond nanoparticles accumulated mainly in the lung, spleen, and liver and were excreted into the urinary tract. The addition of surfactant agents did not lead to significant changes in this pattern, with the exception of a slight reduction in the urinary excretion rate. On the other hand, after filtration of the radiolabeled diamond nanoparticles to remove those with a larger kinetic size, the uptake in the lung and spleen was completely inhibited and significantly reduced in the liver. © 2011 American Chemical Society.
Saez P.,Aragon Institute of Engineering Research |
Saez P.,Research Center Biomedica en Red en Bioingenieria |
Pena E.,Aragon Institute of Engineering Research |
Pena E.,Research Center Biomedica en Red en Bioingenieria |
And 3 more authors.
Computational Mechanics | Year: 2014
Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively. © 2013 Springer-Verlag Berlin Heidelberg.