Staff member

Ignasi Jorba Masdéu

PhD Student
Cellular and Respiratory Biomechanics
+34 934 039 764
Staff member publications

Alcaraz, J., Otero, J., Jorba, I., Navajas, D., (2018). Bidirectional mechanobiology between cells and their local extracellular matrix probed by atomic force microscopy Seminars in Cell and Developmental Biology 73, 71-81

There is growing recognition that the mechanical interactions between cells and their local extracellular matrix (ECM) are central regulators of tissue development, homeostasis, repair and disease progression. The unique ability of atomic force microscopy (AFM) to probe quantitatively mechanical properties and forces at the nanometer or micrometer scales in all kinds of biological samples has been instrumental in the recent advances in cell and tissue mechanics. In this review we illustrate how AFM has provided important insights on our current understanding of the mechanobiology of cells, ECM and cell-ECM bidirectional interactions, particularly in the context of soft acinar tissues like the mammary gland or pulmonary tissue. AFM measurements have revealed that intrinsic cell micromechanics is cell-type specific, and have underscored the prominent role of

Keywords: Atomic force microscopy, Beta1 integrin, Elastic modulus, Extracellular matrix, Morphogenesis, Tissue decellularization

Jorba, I., Uriarte, J. J., Campillo, N., Farré, R., Navajas, D., (2017). Probing micromechanical properties of the extracellular matrix of soft tissues by atomic force microscopy Journal of Cellular Physiology 232, (1), 19-26

The extracellular matrix (ECM) determines 3D tissue architecture and provides structural support and chemical and mechanical cues to the cells. Atomic force microscopy (AFM) has unique capabilities to measure ECM mechanics at the scale at which cells probe the mechanical features of their microenvironment. Moreover, AFM measurements can be readily combined with bright field and fluorescence microscopy. Performing reliable mechanical measurements with AFM requires accurate calibration of the device and correct computation of the mechanical parameters. A suitable approach to isolate ECM mechanics from cell contribution is removing the cells by means of an effective decellularization process that preserves the composition, structure and mechanical properties of the ECM. AFM measurement of ECM micromechanics provides important insights into organ biofabrication, cell-matrix mechanical crosstalk and disease-induced tissue stiffness alterations.

Jorba, I., Menal, M. J., Torres, M., Gozal, D., Piñol-Ripoll, G., Colell, A., Montserrat, J. M., Navajas, D., Farré, R., Almendros, I., (2017). Ageing and chronic intermittent hypoxia mimicking sleep apnea do not modify local brain tissue stiffness in healthy mice Journal of the Mechanical Behavior of Biomedical Materials 71, 106-113

Recent evidence suggests that obstructive sleep apnea (OSA) may increase the risk of Alzheimer´s disease (AD), with the latter promoting alterations in brain tissue stiffness, a feature of ageing. Here, we assessed the effects of age and intermittent hypoxia (IH) on brain tissue stiffness in a mouse model of OSA. Two-month-old and 18-month-old mice (N=10 each) were subjected to IH (20% O2 40 s – 6% O2 20 s) for 8 weeks (6 h/day). Corresponding control groups for each age were kept under normoxic conditions in room air (RA). After sacrifice, the brain was excised and 200-micron coronal slices were cut with a vibratome. Local stiffness of the cortex and hippocampus were assessed in brain slices placed in an Atomic Force Microscope. For both brain regions, the Young's modulus (E) in each animal was computed as the average values from 9 force-indentation curves. Cortex E mean (±SE) values were 442±122 Pa (RA) and 455±120 (IH) for young mice and 433±44 (RA) and 405±101 (IH) for old mice. Hippocampal E values were 376±62 (RA) and 474±94 (IH) for young mice and 486±93 (RA) and 521±210 (IH) for old mice. For both cortex and hippocampus, 2-way ANOVA indicated no statistically significant effects of age or challenge (IH vs. RA) on E values. Thus, neither chronic IH mimicking OSA nor ageing up to late middle age appear to modify local brain tissue stiffness in otherwise healthy mice.

Keywords: Atomic Force Microscopy, Brain mechanics, Cortex stiffness, Hippocampus stiffness, Obstructive sleep apnea, Young's modulus

Marsal, Maria, Jorba, Ignasi, Rebollo, Elena, Luque, Tomas, Navajas, Daniel, Martín-Blanco, Enrique, (2017). AFM and microrheology in the zebrafish embryo yolk cell Journal of Visualized Experiments Developmental Biology, (129), e56224

Elucidating the factors that direct the spatio-temporal organization of evolving tissues is one of the primary purposes in the study of development. Various propositions claim to have been important contributions to the understanding of the mechanical properties of cells and tissues in their spatiotemporal organization in different developmental and morphogenetic processes. However, due to the lack of reliable and accessible tools to measure material properties and tensional parameters in vivo, validating these hypotheses has been difficult. Here we present methods employing atomic force microscopy (AFM) and particle tracking with the aim of quantifying the mechanical properties of the intact zebrafish embryo yolk cell during epiboly. Epiboly is an early conserved developmental process whose study is facilitated by the transparency of the embryo. These methods are simple to implement, reliable, and widely applicable since they overcome intrusive interventions that could affect tissue mechanics. A simple strategy was applied for the mounting of specimens, AFM recording, and nanoparticle injections and tracking. This approach makes these methods easily adaptable to other developmental times or organisms.

Keywords: Developmental Biology, Zebrafish, Yolk, Atomic Force Microscopy, Cortical Tension, Microrheology, Nanoparticle tracking

Campillo, N., Jorba, I., Schaedel, L., Casals, B., Gozal, D., Farré, R., Almendros, I., Navajas, D., (2016). A novel chip for cyclic stretch and intermittent hypoxia cell exposures mimicking obstructive sleep apnea Frontiers in Physiology 7, Article 319

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication, and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS) and consists of a cylindrical well-covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time ~6 s). Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs) exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1a (HIF-1a) expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch.

Keywords: Cell stretch, Hypoxia-inducible factor, Intermittent hypoxia, Lab-on-a-chip, Obstructive sleep apnea