Biology subjects

Dilasser, F.

Publications and source records attributed to Dilasser, F..

3 recordsLinked to original sources

bioRxiv2023

E-cadherin-dependent phosphorylation of EGFR governs a homeostatic feedback loop controlling intercellular junction viscosity and collective migration modes.

Actomyosin tension has been shown to be a ubiquitous driver of tissue morphogenesis1, 2. The Rho pathway, a prominent regulatory network influencing cortical tension, plays a central role in both tissue reorganisation and cell migration3-6. While viscous dissipation in the actin network is commonly regarded as a constant passive parameter in cell migration in both 2D and 3D contexts, there is limited knowledge concerning the regulation of dissipative forces arising from viscous drag between cells during collective rearrangement. Here, we found that the phosphorylation of Epithelial Growth Factor Receptor (EGFR) downstream of de novo E-cadherin adhesion7, 8 orchestrates a feedback loop, thereby governing intercellular viscosity via the Rac pathway regulating actin dynamics. Our findings highlight how the E-cadherin-dependent EGFR activity controls the migration mode of collective cell movements independently of intercellular tension. Combining molecular cell biology, micropatterning, and in silico simulation, our work suggests the existence of a regulatory loop by which cells can tune junctional actin viscosity, with implications for the phenomenology of morphogenetic movements.

cell biology↗

bioRxiv2023

Cortical ductility governs cell-cell adhesion mechanics

This paper challenges our understanding of cell-cell adhesion by emphasising the role of mechanical dissipation at the cellular level. We have developed new microdevices to measure the energy dissipated during the rupture of junctions between cell-cell doublets. Using a synthetic cadherin approach, we decoupled the role of cadherin binding energy, signalling and downstream regulation of cytoskeletal architecture. This yielded a phase diagram in which cell junctions transition from a ductile to a brittle fracture mode based on their ratio of cortical tension and shape relaxation time. We recapitulated our results using a descriptive mechanical simulation approach. Our results shift our understanding of cell-cell adhesion from the current focus on bond energy and tension to the key role played by energy dissipation in the cytoskeleton during junction deformation and its active mechanosensitive regulation.

cell biology↗

bioRxiv2023

Digitalized organoids: integrated pipeline for 3D high-speed analysis of organoid structures using multilevel segmentation and cellular topology

Analysing the tissue morphogenesis and function is crucial for unravelling the underlying mechanisms of tissue development and disease. Organoids, 3D in vitro models that mimic the architecture and function of human tissues, offer a unique opportunity to study effects of external perturbators that are difficult to replicate in vivo. However, large-scale screening procedures for studying the effects of different stress on cellular morphology and topology of these 3D tissue-like system face significant challenges, including limitations in high-resolution 3D imaging, and accessible 3D analysis platforms. These limitations impede the scale and throughput necessary to accurately quantify the effects of mechanical and chemical cues. Here, we present a novel, fine-tuned pipeline for screening morphology and topology modifications in 3D cell culture using multilevel segmentations and cellular topology, based on confocal microscopy and validated across different image qualities. Our pipeline incorporates advanced image analysis algorithms and artificial intelligence (AI) for multiscale 3D segmentation, enabling quantification of morphology changes at both the nuclear and cytoplasmic levels, as well as at the organoid scale. Additionally, we investigate cell relative position and employ neighbouring topology analysis to identify tissue patterning and their correlations with organoid microniches. Eventually, we have organized all the extracted features, 3D segmented masks and raw images into a single database to allow statistical and data mining approaches to facilitate data analysis, in a biologist-friendly way. We validate our approach through proof-of-concept experiments, including well-characterized conditions and poorly explored mechanical stressors such as microgravity, showcasing the versatility of our pipeline. By providing a powerful tool for discovery-like assays in screening 3D organoid models, our pipeline has wide-ranging interests from biomedical applications in development and aging-related pathologies to tissue engineering and regenerative medicine.

cell biology↗