Biology subjects

Di Meglio, I.

Publications and source records attributed to Di Meglio, I..

3 recordsLinked to original sources

bioRxiv2022

Technical insights into fluorescence lifetime microscopy of mechanosensitive Flipper probes

Measuring forces within living cells remains a technical challenge. We developed hydrophobic mechanosensing fluorescent probes called Flippers, whose fluorescence lifetime depends on lipid packing and can report on membrane tension. Here, we describe technical optimization of the probe imaging, and diverse characterizations in various biological and in vitro systems. We provide a guideline to measure biophysical parameters of cellular membranes by FLIM microscopy with Flipper probes, providing evidences that flippers can report long range forces in cells, tissues and organsi.

biophysics↗

bioRxiv2021

Pressure and curvature control of contact inhibition in epithelia growing under spherical confinement

Morphogenesis requires spatiotemporal regulation of cell shape and proliferation, both regulated by biochemical and mechanical cues. In epithelia, this regulation is called contact inhibition, but disentangling biochemical from mechanical cues remains challenging. Here, we show that epithelia growing under confinement accumulate pressure that inhibits proliferation above a threshold value, which depends on the {beta}-catenin pathway. Before inhibition of proliferation, cell aspect ratio abruptly increased upon reaching confluency. This shape transition occurred at low, constant pressure and was mainly controlled by cell density and contractility, correlating with YAP/TAZ pathway inhibition. In our system, epithelia spontaneously buckle: we observed that folding transiently reactivates both the YAP/TAZ pathway and cell proliferation. Altogether, our results support that different mechanical cues part of contact inhibition regulate cell proliferation through different mechanosensing pathways. Proliferation is regulated by sustained, tissue-level pressure through the {beta}-catenin pathway, and by local curvature and pressure changes through the YAP/TAZ pathway.

cell biology↗

bioRxiv2019

Buckling of epithelium growing under spherical confinement

Many organs, such as the gut or the spine are formed through folding of an epithelium. This change in shape is usually attributed to tissue heterogeneities, for example, local apical contraction. In contrast, compressive stresses have been proposed to fold a homogeneous epithelium by buckling. While buckling is an appealing mechanism, demonstrating that it underlies folding requires to measure the stress field and the material properties of the tissue, which is currently inaccessible in vivo. Here we show that monolayers of identical cells proliferating on the inner surface of elastic spherical shells can spontaneously fold. By measuring the elastic deformation of the shell, we infer the forces acting within the monolayer and its elastic modulus. Using analytical and numerical theories linking forces to shape, we find that buckling quantitatively accounts for the shape changes of our monolayers. Our study shows that forces arising from epithelium growth in three-dimensional confinement are sufficient to drive folding by buckling.

biophysics↗