Biology subjects

Hallou, A.

Publications and source records attributed to Hallou, A..

4 recordsLinked to original sources

bioRxiv2023

A computational pipeline for spatial mechano-transcriptomics

Advances in spatial profiling technologies are providing insights into how molecular programs are influenced by local signaling and environmental cues. However, cell fate specification and tissue patterning involve the interplay of biochemical and mechanical feedback. Here, we develop a computational framework that enables the joint statistical analysis of transcriptional and mechanical signals in the context of spatial transcriptomics. To illustrate the application and utility of the approach, we use spatial transcriptomics data from the developing mouse embryo to infer the forces acting on individual cells, and use these results to identify mechanical, morphometric, and gene expression signatures that are predictive of tissue compartment boundaries. In addition, we use geoadditive structural equation modeling to identify gene modules that predict the mechanical behavior of cells in an unbiased manner. This computational framework is easily generalized to other spatial profiling contexts, providing a generic scheme for exploring the interplay of biomolecular and mechanical cues in tissues.

genomics↗

bioRxiv2022

A magnetically actuated, optically sensed tensile testing method for mechanical characterisation of soft biological tissues

Mechanical properties of soft biological tissues play a key role in their normal physiology, contributing to their formation during development, maintenance and repair during adult homeostasis, and driving diseases such as cancer. Mechanics has been proposed to exert its effect by impacting cells fate decisions and cell behaviours including proliferation, differentiation and motility, amongst others. However, despite its critical relevance, a comprehensive analysis of the biomechanics of soft biological tissues is still lacking due to the limitations of the existing characterisation tools. In this article, we describe the development of a device for uniaxial tensile testing of small samples of epithelial and connective tissues, based on the closed-loop interaction between an electromagnetic force actuator and an optical strain sensor. First, we validate the device with synthetic elastomers of known mechanical properties and compare its performance with conventional tensile testing methods; then, we characterise the mechanical properties of the squamous epithelium of the mouse oesophagus along with its supporting connective tissue and underlying muscle in controlled environmental conditions. Through an analysis of strain-stress curves, we demonstrate that the whole oesophagus behaves as a trilayered composite material, whose overall mechanical response depends on the properties of each of its tissue layers. Overall, the proposed setup enables measurements of the mechanical properties of soft biological tissues with unprecedented reliability and precision, and offers an ideal platform for future instrument developments.

biophysics↗

bioRxiv2021

A biomechanical switch regulates the transition towards homeostasis in esophageal epithelium

Epithelial cells are highly dynamic and can rapidly adapt their behavior in response to tissue perturbations and increasing tissue demands. However, the processes that finely control these responses and, particularly, the mechanisms that ensure the correct switch to and from normal tissue homeostasis are largely unknown. Here we explore changes in cell behavior happening at the interface between postnatal development and homeostasis in the epithelium of the mouse esophagus, as a physiological model exemplifying a rapid but controlled tissue growth transition. Single cell RNA sequencing and histological analysis of the mouse esophagus reveal significant mechanical changes in the epithelium upon tissue maturation. Organ stretching experiments further indicate that tissue strain caused by the differential growth of the mouse esophagus relative to the entire body promotes the emergence of a defined committed population in the progenitor compartment as homeostasis is established. Our results point to a simple mechanism whereby the mechanical changes experienced at the whole tissue level are integrated with those "sensed" at the cellular level to control epithelial cell behavior and tissue maintenance.

cell biology↗

bioRxiv2018

Theory of mechano-chemical patterning in biphasic biological tissues

The formation of self-organized patterns is key to the morphogenesis of multicellular organisms, although a comprehensive theory of biological pattern formation is still lacking. Here, we propose a biologically realistic and unifying approach to emergent pattern formation. Our biphasic model of multicellular tissues incorporates turnover and transport of morphogens controlling cell differentiation and tissue mechanics in a single framework, where one tissue phase consists of a poroelastic network made of cells and the other is the extracellular fluid permeating between cells. While this model encompasses previous theories approximating tissues to inert monophasic media, such as Turings reaction-diffusion model, it overcomes some of their key limitations permitting pattern formation via any two-species biochemical kinetics thanks to mechanically induced cross-diffusion flows. Moreover, we unravel a qualitatively different advection-driven instability which allows for the formation of patterns with a single morphogen and which single mode pattern scales with tissue size. We discuss the potential relevance of these findings for tissue morphogenesis.

biophysics↗