Biology subjects

Buceta, J.

Publications and source records attributed to Buceta, J..

8 recordsLinked to original sources

bioRxiv2025

3DTubularVoronoi: a Voronoi-Based Framework for Estimating Equilibrium Cellular Packing in 3D Tubular Epithelia

Epithelial tube morphogenesis is fundamental to organ development and functioning, yet accurately modeling its intricate 3D organization and dynamics remains a challenge. In particular, current computational tools fail to capture the spontaneous emergence of non-transient scutoids, a geometric feature essential for accommodating curvature in epithelia. Here, we introduce 3DTubularVoronoi, a novel simulation framework for modeling epithelial tube morphogenesis and determining their stable cell packing organization depending on mechanical parameters. The model employs a Voronoi tessellation strategy combined with an energy minimization approach using the Metropolis-Hasting algorithm. 3DTubularVoronoi enables realistic epithelial tube simulations, accounting for scutoid formation and dynamic rearrangements. This tool provides an open-source, user-friendly solution for exploring gland morphogenesis and offering insights into developmental biology and tissue engineering. Availabilityhttps://github.com/TheSiMBioSysI2SysBio/3DTubularVoronoi

bioinformatics↗

bioRxiv2025

Spatial dynamics and emergent properties of pLS20 conjugation on solid surfaces

Horizontal gene transfer (HGT) is a major evolutionary process in bacteria, driving the dissemination of genetic traits including antibiotic resistance (AR). In this study, we employ a hybrid modeling approach, combining agent-based simulations and Ordinary Differential Equation (ODE) models, to investigate bacterial conjugation--a key HGT mechanism whose dynamics remain poorly understood. Our agent-based simulations of the transfer dynamics of the conjugative plasmid pLS20 from Bacillus subtilis reveal that spatial organization, colony growth dynamics, and quorum-sensing regulation significantly influence plasmid dissemination. Increased donor-recipient mixing enhances plasmid transmission by reducing quorum-induced repression, while colony growth-driven displacement of donor cells alters the local distribution of quorum-sensing signals, enabling sustained conjugation activity at the colony periphery. Complementary ODE modeling captures macroscopic trends in plasmid transmission, providing insights into the interplay between spatial factors and regulatory mechanisms. By bridging single-cell regulatory dynamics with population-level behaviors, this study advances our understanding of bacterial conjugation on solid surfaces, offering potential strategies for mitigating the spread of antibiotic resistance. Author summaryBacteria can exchange genetic material through a process called horizontal gene transfer, which helps them adapt to new environments but also develop traits like antibiotic resistance. One of the most important ways bacteria share genes is through conjugation--a mechanism where a conjugative element transfers from a donor to a recipient via a channel connecting both cells. Although considerable knowledge has been gathered over the last decades concerning regulation of the conjugation genes and the structure of the transferosome responsible for transfer of the conjugative element, far less is known about the dynamics of conjugative transfers within populations of cells, especially on solid medium. Our study focuses on the conjugative plasmid pLS20 from Bacillus subtilis, a model bacterium related to several pathogens. Using computer simulations, we modeled how this plasmid spreads within bacterial colonies growing on solid surfaces. We found that the spatial organization of bacteria plays a large role: well-mixed populations allow the plasmid to spread more effectively, while certain growth patterns disrupt the signaling processes that regulate gene transfer. This study helps us better understand how bacteria transfer genes in complex environments and could guide new strategies to combat antibiotic resistance.

systems biology↗

bioRxiv2025

Mechanical strain modulates Min patterning and division in E. coli filaments

Bacteria often encounter physico-chemical stresses that disrupt division, leading to filamentation, where cells elongate without dividing. While this adaptive response enhances survival, it also exposes filaments to significant mechanical strain, raising questions about the mechanochemical feedback in bacterial systems. In this study, we investigate how mechanical strain influences the Min oscillatory system, a reaction-diffusion network central to division in Escherichia coli. Through a multidisciplinary approach combining quantitative fluorescence microscopy, biophysical modeling, microfluidics, and patterned growth substrates, we demonstrate that filamentous E. coli undergoes growth-induced buckling instability. This phenomenon alters the diffusivity of membrane proteins and modulates the spatiotemporal patterning of the Min system. Moreover, we show that this mechanochemical interplay determines division site positioning after stress relief, effectively creating a mechanical "memory" for cytokinesis. Our findings underscore the critical role of mechanical forces in bacterial filamentation and provide new insights into the functional implications of mechanobiology in microbial systems.

biophysics↗

bioRxiv2022

Comprehensive profiling of polyclonal sera targeting a non-enveloped viral capsid

Despite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targeting the capsid of a prototypical picornavirus. Our results uncover significant variation in the breadth and strength of neutralization sites targeted by individual human polyclonal responses, which contrasted with homogenous responses observed in experimentally infected mice. We further use these comprehensive antigenic profiles to define key structural and evolutionary parameters that are predictive of escape, assess epitope dominance at the population level, and reveal a need for at least two mutations to achieve significant escape from multiple sera. Overall, our data provide the first comprehensive analysis of how polyclonal sera target a non-enveloped viral capsid and help define both immune dominance and escape at the population level.

microbiology↗

bioRxiv2020

Mycobacterium phage Butters-encoded proteins contribute to host defense against viral attack

A diverse set of prophage-mediated mechanisms protecting bacterial hosts from infection has been recently uncovered within Cluster N mycobacteriophages. In that context, we unveil a novel defense mechanism in Cluster N prophage Butters. By using bioinformatics analyses, phage plating efficiency experiments, microscopy, and immunoprecipitation assays, we show that Butters genes located in the central region of the genome play a key role in the defense against heterotypic viral attack. Our study suggests that a two component system articulated by interactions between protein products of genes 30 and 31 confers defense against heterotypic phage infection by PurpleHaze or Alma, but is insufficient to confer defense against attack by the heterotypic phage Island3. Therefore, based on heterotypic phage plating efficiencies on the Butters lysogen, additional prophage genes required for defense are implicated. IMPORTANCEMany sequenced bacterial genomes including pathogenic bacteria contain prophages. Some prophages encode defense systems that protect their bacterial host against heterotypic viral attack. Understanding the mechanisms undergirding these defense systems will be critical to development of phage therapy that circumvents these defenses. Additionally, such knowledge will help engineer phage-resistant bacteria of industrial importance.

microbiology↗

bioRxiv2020

A quantitative principle to understand 3D cellular connectivity in epithelial tubes

Epithelial cell organization and the mechanical stability of tissues are closely related. In this context, it has been recently shown that packing optimization in bended/folded epithelia is achieved by a surface tension energy minimization mechanism that leads to a novel cellular shape: the scutoid. However, further cellular and tissue level implications of this new developmental paradigm remain unknown. Here we focus on the relationship between this complex cellular shape and the connectivity between cells. We address this problem using a combination of computational, experimental, and biophysical approaches in tubular epithelia. In particular, we examine how energy drivers affect the three-dimensional packing of these tissues. We challenge our biophysical model by reducing the cell adhesion in epithelial cells. As a result, we observed an increment on the cell apico-basal intercalation propensity that correlated with a decrease of the energy barrier necessary to connect with new cells. We conclude that tubular epithelia satisfy a quantitative biophysical principle, that links tissue geometry and energetics with the average cellular connectivity.

developmental biology↗

bioRxiv2020

TiFoSi: an Efficient Tool for Mechanobiology Simulations of Epithelia

AboutThis document is an extended version of the main text where some details and results are fleshed out. Further details can be also found in the manual of the code and at TiFoSis website: http://tifosi.thesimbiosys.com. MotivationEmerging phenomena in developmental biology and tissue engineering are the result of feedbacks between gene expression and cell biomechanics. In that context, in silico experiments are a powerful tool to understand fundamental mechanisms and to formulate and test hypotheses. ResultsHere we present TiFoSi, a computational tool to simulate the cellular dynamics of planar epithelia. TiFoSi allows to model feedbacks between cellular mechanics and gene expression (either in a deterministic or a stochastic way), the interaction between different cell populations, the custom design of the cell cycle and cleavage properties, the protein number partitioning upon cell division, and the modeling of cell communication (juxtacrine and paracrine signalling). TiFoSi fills a niche in the field of software solutions to simulate the mechanobiology of epithelia because of its functionalities, computational efficiency, and its user-friendly approach to design in silico experiments using XML configuration files. Availabilityhttp://tifosi.thesimbiosys.com Contactjbuceta@lehigh.edu

systems biology↗

bioRxiv2019

Self-sustained Planar Intercalations due to Mechanosignaling Feedbacks Lead to Robust Axis Extension during Morphogenesis

Tissue elongation is a necessary process in metazoans to implement their body plans that is not fully understood. Here we propose a mechanism based on the interplay between cellular mechanics and primordia patterning that results in self-sustained planar cell intercalations. Thus, we show that a location-dependent modulation of cell mechanics due to positional information leads to robust axis extension. To illustrate the plausibility of this model, we use different experimentally reported patterning mechanisms in simulations that implement mechano-signaling feedback. Our results suggest that robust elongation relies on a trade-off between cellular and tissue strains that is orchestrated via the cleavage orientation. In the particular context of axis extension in Turing-patterned primordia we report that the combination of different directional cell activities lead to synergetic effects. Altogether, our findings help to understand how the emerging phenomenon of tissue elongation emerges from the individual cell dynamics.

systems biology↗