Biology subjects

Torro, R.

Publications and source records attributed to Torro, R..

7 recordsLinked to original sources

bioRxiv2026

Multiscale oocyst wall mechanics govern coccidian resistance

Coccidian parasites spread through oocysts, environmental transmission stages that must survive harsh conditions yet rupture on cue inside the host to release infectious sporozoites. How the oocyst wall reconciles these opposing demands is unknown. Using single-oocyst microindentation, quantitative imaging and infection assays in Eimeria acervulina and Eimeria tenella, we show that the bilayered wall is functionally partitioned: the chemically fragile outer layer is mechanically dispensable, while the inner layer bears the mechanical load and remains impermeable to macromolecules and limiting osmotic exchange even after the outer layer is stripped. Oocysts behave as pressurised shells that fail preferentially at the anterior pole, a fixed mechanical weak point that channels sporocyst release regardless of where force is applied. Wall structure, autofluorescence, mechanics and infectivity prove dissociable: bleach removes the outer layer without weakening the wall or fully abolishing infectivity, whereas heat weakens the wall and abolishes infectivity while leaving the bilayered structure intact. These findings define a mechanical logic for coccidian oocyst resistance, disinfection and controlled excystation, and identify the inner wall as the critical target for inactivating environmentally transmitted parasites.

microbiology↗

bioRxiv2026

Antibody maturation in germinal centers selects mutants based on BCR-antigen bond mechanical resistance

Antibody maturation in germinal centers (GCs) is traditionally viewed as a process that enhances antigen-binding affinity of B cell receptors (BCR). However, recent studies challenge this paradigm, revealing no systematic antibody affinity improvement during GC selection. Here, we investigate whether mechanical resistance of antibody-antigen bonds, rather than affinity, is the selective parameter driving GC maturation. Using biolayer interferometry measurements for assessing affinity and laminar flow chamber for mechanical resistance, we analyzed three lineages of mouse antibodies generated after immunization with ovalbumin. While affinity changes were heterogeneous, ranging from gains to losses across lineages, mechanical resistance consistently increased after maturation. Bond lifetimes under physiological forces (10-70 pN) converged to similar values across lineages, suggesting a selective pressure for mechanical stability. Functionally, NK cell activation in a surrogate in vitro ADCC assay correlated with bond lifetimes under force, but not with affinity. This indicates that lymphocytes are sensitive to the mechanical stability of antibody-antigen interactions, which may underlie GC selection. Our findings reconcile antibody maturation with the idea of enhanced binding, while aligning with the role of mechanical forces in B cell signaling and antigen uptake. These insights provide a framework for understanding GC biology and may inform the design of therapeutic antibodies.

immunology↗

bioRxiv2025

Smart Microscopy: Current Implementations and a Roadmap for Interoperability

Smart microscopy is transforming life sciences by automating experimental imaging workflows and enabling real-time adaptation based on feedback from images and other data streams. This shift increases throughput, improves reproducibility, and expands the functional capabilities of microscopes. However, the current landscape is highly fragmented. Academic researchers often develop custom solutions for specific scientific needs, while industry offerings are typically proprietary and tied to specific hardware. This diversity, while fostering innovation, also creates major challenges in interoperability, reproducibility, and standardization, which slows progress and adaption. This article presents a collaborative effort between academic and industry leaders to survey the current state of smart microscopy, highlight representative implementations, and identify common technical and organizational barriers. We propose a framework for greater interoperability based on shared standards, modular software design, and community-driven development. Our goal is to support collaboration across the field and lay the groundwork for a more connected, reusable, and accessible smart microscopy ecosystem. We conclude with a call to action for researchers, hardware developers, and institutions to join in building an open, interoperable foundation that will unlock the full potential of smart microscopy in life science research.

cell biology↗

bioRxiv2024

Celldetective: an AI-enhanced image analysis toolfor unraveling dynamic cell interactions

Analysis of multimodal and multidimensional data capturing dynamic interactions between diverse cell populations is a current challenge in bioimaging, especially in the context of immunology and immunotherapy research. Here, we introduce Celldetective, an open-source Python-based software tool designed for high-performance, end-to-end analysis of image-based in vitro immune and immunotherapy assays. Celldetective is purpose-built for multicondition, 2D multi-channel time-lapse microscopy of mixed cell populations. Although it is optimised for the needs of immunology assays, it is nevertheless broadly applicable to any biological system involving interacting cell populations. The software seamlessly integrates AI-based segmentation, tracking, and automated single-cell event detection, all within an intuitive graphical interface that supports interactive visualisation, annotation, and training options. We showcase its capabilities with original datasets of single immune effector cell interactions with an activating surface mediated by bispecific antibodies, and pairwise interactions in antibody-dependent cell cytotoxicity events.

bioinformatics↗

bioRxiv2024

Antigen density and applied force control enrichment of nanobody-expressing yeast cells in microfluidics

In vitro display technologies such as yeast display have been instrumental in developing the selection of new antibodies, antibody fragments or nanobodies that bind to a specific target, with affinity towards the target being the main factor that influences selection outcome. However, the roles of mechanical forces are being increasingly recognized as a crucial factor in the regulation and activation of effector cell function. It would thus be of interest to isolate binders behaving optimally under the influence of mechanical forces. We developed a microfluidic assay allowing the selection of yeast displaying nanobodies through antigen-specific immobilization on a surface under controlled hydrodynamic flow. This approach enabled enrichment of model yeast mixtures using tunable antigen density and applied force. This new force-based selection method opens the possibility of selecting binders by relying on both their affinity and force resistance, with implications for the design of more efficient immunotherapeutics.

bioengineering↗

bioRxiv2023

Establishment of Wnt ligand-receptor organization and cell polarity in the C. elegans embryo

Different signaling mechanisms concur to ensure robust tissue patterning and cell fate instruction during animal development. Most of these mechanisms rely on signaling proteins that are produced, transported and detected. The spatiotemporal dynamics of signaling molecules is largely unknown, yet it determines signal activitys range and time frame. Here, we use the Caenorhabditis elegans embryo to study how Wnt ligands, an evolutionarily conserved family of signaling proteins, dynamically organize to establish cell polarity in a developing tissue. We identify how locally produced Wnt ligands spread to transmit information to distant target cells. With quantitative live imaging, we show that the Wnt ligands diffuse extracellularly through the embryo over a timescale shorter than the cell cycle. We extract diffusion coefficients of Wnt ligands and their receptor Frizzled (Fz) and characterize their co-localization. Integrating our different measurements and observations in a simple computational framework, we show how fast diffusion in the embryo can polarize target cells. Our results support diffusion-based long-range Wnt signaling, which is consistent with the dynamics of developing processes.

developmental biology↗

bioRxiv2022

Cellular forces during early spreading of T lymphocytes on ultra-soft substrates

Mechanical forces are increasingly recognized as critical regulators of T cell activation, yet their earliest dynamics remain poorly resolved. Here, we use traction force microscopy on ultra-soft, antigen-presenting-cell-like polyacrylamide substrates to quantify the first 15 minutes of force generation by Jurkat and primary human CD4 T cells under controlled activating conditions. By combining time-resolved stress mapping with spatial tensor analysis, we uncover previously unrecognized heterogeneity in early T cell mechanosensing. Rather than producing a single stereotyped mechanical response, T cells exhibit three distinct temporal force regimes: low-amplitude active fluctuations, intermittent force bursts, and sustained sigmoidal buildups of stress. These temporal programs tightly couple to spatial organization: fluctuating and intermittent behaviors associate with disordered stress distributions, whereas sustained sigmoidal responses predominantly accompany polarized, dipolar, and unexpectedly extensile stress patterns. Substrate stiffness strongly reshapes this distribution, with stiffer gels suppressing sustained high-energy responses and biasing cells toward fragmented mechanical engagement. Primary T cell subsets likewise display distinct force phenotypes: naive cells exhibit weak, fluctuating behaviors, whereas memory cells more readily enter sustained high-force states. Together, these findings support a two-stage model of early T cell mechanosensing in which filopodia-mediated probing generates low, intermittent forces that, upon sustained engagement, transition to a lamellipodia-driven spreading phase producing larger, persistent, and predominantly outward-directed stresses. This framework provides a mechanistic explanation for how substrate mechanics, receptor context, and immune cell state shape force generation during the earliest stages of activation. More broadly, our results identify force as a dynamic and structured component of antigen recognition rather than a passive consequence of T cell signaling. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/480084v4_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@29e24dorg.highwire.dtl.DTLVardef@1c8399forg.highwire.dtl.DTLVardef@3f29edorg.highwire.dtl.DTLVardef@d9a581_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗