Biology subjects

Davit, Y.

Publications and source records attributed to Davit, Y..

4 recordsLinked to original sources

bioRxiv2026

A mechanical model of multicellular remodelling in epithelial monolayers

Epithelial monolayers are the foundation of many mammalian organs and have a significant impact on numerous biological processes, including the secretion of cytokines, absorption of waste products and barrier function. During organ development epithelia are subject to many external forces due to the growth of the surrounding tissues. They exhibit complex responses to such forces, with deformation occurring on short timescales (seconds), and relaxation and remodelling occurring on longer timescales (minutes or hours). Existing mathematical and computational models do not typically account for subcellular remodelling, assuming instead that the response to an applied force or strain acts on a single timescale. In this paper we extend an off-lattice, cell-centre modelling framework to account for subcellular and tissue remodelling by introducing a Dynamic Reference Frame (DRF). The DRF provides a discrete, cell-based analogue of morpho-elasticity: it decouples the evolution of each cell's mechanical reference configuration from its instantaneous deformation, providing a phenomenological description of subcellular remodelling processes - cytoskeletal reorganisation, myosin turnover and adhesion bond remodelling - at the cellular scale. Using this extended multicellular model, we reproduce multiscale responses to external mechanical forces, including creep and stress relaxation experiments, and demonstrate that the history of applied deformation influences tissue recovery upon release. Additionally we identify and quantify where and how these multiscale responses occur. The resulting framework allows for more detailed descriptions and analyses of the development and function of biological tissues.

biophysics↗

bioRxiv2026

Oxygen gradients reshape cross-feeding through emergent spatial organization of gut commensal bacteria

Microbial interactions unfold within environments structured by physical transport and chemical gradients. Yet most mechanistic studies rely on well-mixed systems that mask the reciprocal influences of environmental heterogeneity on metabolism and ecology. Here, we investigate how the physical environment modulates the interaction between the gut commensal Bacteroides thetaiotaomicron and Escherichia coli. In anoxic liquid culture, cell-resolved isotope imaging and genetic perturbations reveal exploitative cross-feeding, where E. coli consumes diffusible sugars released by B. thetaiotaomicron during starch degradation. When exposed to intestinal-like oxygen gradients in microfluidics, the interaction is restructured by spatial organization. The species self-organize into complementary niches: E. coli locally depletes sugars and oxygen, thereby expanding the anoxic niche required by B. thetaiotaomicron. A reactive transport model confirms that this organization arises from coupled feedback between physical transport and metabolic reaction rates. Together, our results reveal how physical structure and chemical gradients convert an exploitative cross-feeding interaction into a dynamic niche-construction process that generates emergent spatial organization and stabilizes coexistence.

microbiology↗

bioRxiv2024

Should I stay or should I go? Spatio-temporal dynamics of bacterial biofilms in confined flows

Most bacteria live in sessile biofilms that colonize the confined channels, pores and crevices of natural and engineered structures. In these environments, flow delivers nutrients necessary for growth while simultaneously generating mechanical stresses that cause detachment from surfaces. Bacteria, in turn, colonize flow passages, increasing hydraulic resistance and modifying transport properties. Although the importance of advective transport and hydrodynamic forces on bacterial populations is well established, the complex feedback mechanisms governing biofilm development in confined geometries remain poorly understood. Here, we study how couplings between flow and bacterial development control the spatiotemporal dynamics of Pseudomonas aeruginosa in microchannel flows. We demonstrate that nutrient availability primarily drives the longitudinal distribution of biomass along the channel, while competition between growth and flow-induced detachment controls the transverse distribution and temporal dynamics. We find that biofilms undergo successive cycles of sloughing and regrowth, causing persistent fluctuations in the hydraulic resistance and biomass that prevent the system from ever reaching a true steady state. Our results indicate that these self-sustained fluctuations are a signature effect in confined flows, originating from a pressure build-up as growing bacteria obstruct flow paths. We further show that the sloughing dynamics can be described as a jump stochastic process with gamma-distributed interevent times, analogous to other bursting events such as earthquakes or avalanches. This stochastic framework provides a quantitative approach to characterizing the inherent randomness and apparent irreproducibility of biofilm experiments, opening new avenues for predictive modeling of biofilms in confined systems.

biophysics↗

bioRxiv2017

Neutrophil adhesion in brain capillaries contributes to cortical blood flow decreases and impaired memory function in a mouse model of Alzheimer’s disease

The existence of cerebral blood flow (CBF) reductions in Alzheimers disease (AD) patients and related mouse models has been known for decades, but the underlying mechanisms and the resulting impacts on cognitive function and AD pathogenesis remain poorly understood. In the APP/PS1 mouse model of AD we found that an increased number of cortical capillaries had stalled blood flow as compared to wildtype animals, largely due to leukocytes that adhered in capillary segments and blocked blood flow. These capillary stalls were an early feature of disease development, appearing before amyloid deposits. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to an immediate increase in CBF and to rapidly improved performance in spatial and working memory tasks. Our work has thus identified a cellular mechanism that explains the majority of the CBF reduction seen in a mouse model of AD and has also demonstrated that improving CBF rapidly improved short-term memory function. Restoring cerebral perfusion by preventing the leukocyte adhesion that plugs capillaries may provide a novel strategy for improving cognition in AD patients.

neuroscience↗