Biology subjects

Jurado, A.

Publications and source records attributed to Jurado, A..

6 recordsLinked to original sources

bioRxiv2026

Zebrafish embryos are robust to mechanical perturbations

The investigation of morphogenesis during organism development has massively benefited from the interaction between developmental biology and biophysics, which gave new quantitative insights into natures physical working principles. The process of zebrafish epiboly provides a beautiful model system as cells exhibit collective migration, meanwhile requiring symmetry breaking for gastrulation and the subsequent tissue differentiation. These elegantly robust processes are facilitated by both biochemical and mechanical cues. Here we test the hypothesis that the future body axis is robust against mechanical perturbations of tissue flow and tissue stress fields. For this, we trigger tissue flow by photoablation, which leads to an externally enforced symmetry breaking before natural symmetry breaking of gastrulation occurs. Using 3D light sheet microscopy, we obtained nuclei trajectories as a proxy for the migration of individual cells. Analyzing the derived tissue velocity field, we observed that epiboly is highly robust and mostly unaffected by ablation damage. However, the photoablation induced a convergent motion of cells towards an azimuthal angle resembling shield formation. We extensively characterized this convergent motion and checked if this tissue flow is able to reorient natural symmetry breaking during shield formation. While ablations can transiently disrupt or reorient the convergent motion, we cannot confirm any redirection of the location where the future body axis of the animal develops. The observations were also highly dependent on the developmental stage of the embryo, which cast a greater and more permanent impact, suggesting strong control exerted by factors other than mechanical signals. Significance statementMorphogenesis emerges from the interplay between biochemical patterning and mechanical forces, yet the extent to which mechanical cues influence embryo developmental remains unclear. Using zebrafish epiboly as model system, we imposed controlled mechanical perturbations through targeted photoablation and tracking resulting 3D cell movements. We show that although ablations generate transient convergent motions, epiboly is remarkably robust to externally induced tissue flows. Our findings indicate that the future body axis is strongly buffered against mechanical disturbances, highlighting the dominant role of developmental stage and non-mechanical cues in guiding development.

biophysics↗

bioRxiv2025

Intermittent Hypoxia Drives Early Metabolic Dysfunction in Brown Adipose Tissue

BackgroundObstructive sleep apnea (OSA) is associated with metabolic dysfunction, yet the early impact of intermittent hypoxia (IH)--a defining feature of OSA--on brown adipose tissue (BAT) remains unclear. MethodsWe investigated the direct and early effects of IH on BAT using both in vitro and in vivo approaches. Differentiated mouse brown adipocytes were exposed to IH for 48 hours and analyzed for {beta}3-adrenergic signaling, lipolysis, and thermogenic activation. Complementary in vivo studies assessed transcriptomic, morphological, and functional changes in BAT, white adipose tissue (WAT), and liver after 1 or 4 weeks of IH exposure in mice. ResultsIH blunted {beta}3-adrenergic signaling in cultured brown adipocytes, leading to reduced phosphorylation of key signaling proteins, impaired lipolytic response, and decreased expression of UCP1. In vivo, BAT exhibited early and sustained transcriptomic rewiring characterized by downregulation of pathways related to fatty acid metabolism, oxidative phosphorylation, and peroxisomal function. These molecular changes were accompanied by abnormal lipid droplet enlargement and a reduced lipolytic response to adrenergic stimulation. In contrast, WAT showed transient gene expression changes, and the liver displayed a delayed and robust transcriptomic response evident only after four weeks of IH exposure. Despite these metabolic alterations, thermogenic responses to cold challenge remained intact in IH-treated mice. ConclusionsBAT is uniquely and rapidly affected by intermittent hypoxia, undergoing functional, molecular, and morphological changes within one week of exposure. These alterations precede systemic inflammation and metabolic dysfunction, positioning BAT dysfunction as an early event in the pathogenesis of OSA-associated metabolic disease.

pathology↗

bioRxiv2023

Reaching the tumor: mobility of polymeric micelles inside an in vitro tumor-on-a-chip model with dual ECM

Degradable polymeric micelles are promising drug delivery systems due to their hydrophobic core and responsive design. When applying micellar nanocarriers for tumor delivery, one of the bottlenecks encountered in vivo is the tumor tissue barrier - crossing the dense mesh of cells and extracellular matrix (ECM). Sometimes overlooked, the extracellular matrix can trap nanoformulations based on charge, size and hydrophobicity. Here we used a simple design of a microfluidic chip with two types of ECM and MCF7 spheroids to allow "high throughput" screening of the interactions between biological interfaces and polymeric micelles. To demostrarte the applicapility of the chip, a small library of fluorescently labelled polymeric micelles varying in their hydrophilic shell and hydrophobic core forming blocks was studied. Three widely used hydrophilic shells were tested and compared, poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid), along with two enzyamticaly degradable dendritic hydrophobic cores (based on Hexyl or Nonyl end-gorups). Using ratiometric imaging of unimer:micelle fluorescence and FRAP inside the chip model, we obtained the local assembly state and dynamics inside the chip. Notably, we observed different micelle behaviors in the basal lamina ECM, from avoidance of ECM structure to binding of the poly(acrylic acid) formulations. Binding to basal lamina correlated with higher uptake into MCF7 spheroids. Overall, we proposed a simple microfluidic chip containing dual ECM and spheroids for the assessment of the interactions of polymeric nanocarrires with biological interfaces and evaluating nanoformulations capacity to cross the tumor tissue barrier.

bioengineering↗

bioRxiv2021

Pressure drives rapid burst-like collective migration from 3D cancer aggregates

Collective migration of cells is a key behaviour observed during morphogenesis, wound healing and cancer cell invasion. Hence, understanding the different aspects of collective migration is at the core of further progress in describing and treating cancer and other pathological defects. The standard dogma in cell migration is that cells exert forces on the environment to move and cell-cell adhesion-based forces provide the coordination for collective migration. Here, we report a new collective migration mechanism that is independent of pulling forces on the extra-cellular matrix (ECM), as it is driven by the pressure difference generated inside model tumours. We observe a striking collective migration phenotype, where a rapid burst-like stream of HeLa cervical cancer cells emerges from the 3D aggregate embedded in matrices with low collagen concentration (0.5 mg ml-1). This invasion-like behaviour is recorded within 8 hours post embedding (hpe), and is characterised by high cell velocity and super-diffusive collective motion. We show that cellular swelling, triggered by the soft matrix, leads to a rise in intrinsic pressure, which eventually drives an invasion-like phenotype of HeLa cancer aggregates. These dynamic observations provide new evidence that pressure-driven effects need to be considered for a complete description of the mechanical forces involved in collective migration and invasion.

biophysics↗

bioRxiv2020

Global and local tension measurements in biomimetic skeletal muscle tissues reveals early mechanical homeostasis

The mechanical properties and tension of muscle tissue are tightly related to proper skeletal muscle function, which makes experimental access to the biomechanics of muscle tissue development a key requirement to advance our understanding of muscle function and development. Recently developed elastic in vitro culture chambers allow for raising 3D muscle tissue under controlled conditions and measurements of tissue force generation. However, these chambers are inherently incompatible with high resolution microscopy limiting their usability to global force measurements, and preventing the exploitation of modern fluorescence based investigation methods for live and dynamic measurements. Here we present a new chamber design pairing global force measurements, quantified from post deflection, with local tension measurements obtained from elastic hydrogel beads embedded in the muscle tissue. High resolution 3D video microscopy of engineered muscle development, enabled by the new chamber, shows an early mechanical tissue homeostasis that remains stable in spite of continued myotube maturation.Competing Interest StatementTB and AH have filed a patent for the presented chamber system.View Full Text

biophysics↗

bioRxiv2020

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV. Significance statementZika virus (ZIKV) infection during pregnancy can cause fetal abnormalities. Vaccines against ZIKV are under development, but because of potential safety concerns due to disease enhancing antibodies, and the time required by active immunization to induce protective antibodies, there is a need to explore alternative strategies. Recombinant monoclonal antibodies can be modified to prevent enhancement of infection, and thus could be an efficacious and safe alternative to vaccines to confer rapid protection. We show that prophylactic administration of two engineered antibodies, Z004 and Z021, to pregnant macaques partially protects against fetal neurologic damage and limits vertical transmission of ZIKV.

immunology↗