Biology subjects

Merle, T.

Publications and source records attributed to Merle, T..

5 recordsLinked to original sources

bioRxiv2026

Deep-tissue absolute force spectroscopy with sub-piconewton precision

Quantitative measurements performed directly in vivo are necessary to understand how forces shape living tissues, yet this remains challenging due to optical scattering and mechanical complexity. Here, we present a method for making absolute force measurements using nanoscopic optical tweezers with a sensitivity of 300 fN in optically turbid biological media. Our approach combines back focal plane interferometry operating within the optical memory effect regime with a global fluctuation-dissipation fitting framework that simultaneously calibrates position detection, trap stiffness, and viscoelastic response. This method overcomes aberration-induced biases by jointly fitting passive fluctuations and driven harmonic responses, enabling robust force reconstruction in thick, scattering tissues within the mechanically relevant frequency range below 300 Hz. We validate our approach using highly scattering Drosophila pupae and embryos, demonstrating reliable in vivo measurements of forces and mechanical properties. Operating at a 1 kHz acquisition bandwidth, the system captures relevant mechanical dynamics without requiring extended high-frequency detection. Using this framework, we quantify the increase in cortical tension during pupal morphogenesis, characterize tissue viscoelasticity, and reveal stage-dependent variations in nuclear membrane tension during embryogenesis, even in the presence of strong ATP-driven fluctuations. Beyond bulk measurements, our method enables the quantitative mechanical characterization of single cells within mechanically coupled tissues.

bioengineering↗

bioRxiv2025

Spatio-temporal control of nuclear mechanotransduction during EMT

During epithelial-to-mesenchymal transition (EMT), cells generate mechanical forces. How the nucleus reacts to these mechanical cues, ensuring a tight balance between mechano-protection and mechanotransduction, is a key yet unresolved question. Here we dissect the spatio-temporal control of nuclear mechanostransduction during EMT, using Drosophila mesoderm invagination as a model. We found that two conserved pro-EMT genes respond differently to compressive forces: while snail transcription remains unaffected, compression is sufficient to activate twist transcription within seconds. We further revealed a spatially patterned genome-wide transcriptional response to EMT forces, with an apical mechanoprotection contrasting with a permissive basal nuclear environment. The direct recording of nascent transcription in response to a controlled nuclear micromanipulation provides compelling evidence of nuclear heterogeneity in the transcriptional response to forces. Overall, these results reveal that EMT nuclei respond directly and rapidly to mechanical forces, in a spatially defined pattern.

cell biology↗

bioRxiv2024

Compressive stress drives morphogenetic apoptosis

Tissues and organs are constantly submitted to physical stress, including compression, stretching, shear stress. The impact of compression due to overcrowding on cell extrusion has been the focus of recent studies. However, how tissue compression impact cell death in the context of morphogenesis is mostly unexplored. Here, we showed that a natural compression is exerted on the Drosophila developing leg by the surrounding tissue (or envelope) that is required for correct leg morphogenesis. In this tissue, apoptosis, preferentially localized in the future fold region, contributes to drive tissue folding through the generation of a pulling force on the apical surface. However, only a subset of these cells are dying within the expression domain of proapoptotic genes and how this precise pattern of cell death is established is totally unknown. We found that the natural compression exerted by the envelope contributes to the regulation of apoptosis, revealing that compression constitutes an integral part of apoptosis regulation during leg morphogenesis. We further reveal that compression drives a significant increase in lateral tension and favors apoptosis through the mechanosensor Piezo. Finally, perturbing cell cortex anchoring or membrane stiffness prove sufficient to block this process. Altogether, these results open new perspectives in term of mechanotransduction during morphogenesis.

developmental biology↗

bioRxiv2023

An easy-to-use microfluidic mechano-chemostat for tissues and organisms reveals that confined growth is accompanied with increased macromolecular crowding

Conventional culture conditions are oftentimes insufficient to study tissues, organisms, or 3D multicellular assemblies. They lack both dynamic chemical and mechanical control over the microenvironment. While specific microfluidic devices have been developed to address chemical control, they are often hard to use and do not allow the control of compressive forces. Here, we present a set of microfluidic devices which all rely on the use of sliding elements consisting of microfabricated rods that can be inserted inside a microfluidic device. Sliding elements enable the creation of reconfigurable sealed culture chambers for the study of whole organisms or model micro-tissues. By confining the micro-tissues, we studied the biophysical impact of growth-induced pressure and showed that this mechanical stress is associated with an increase in macromolecular crowding, shedding light on this understudied type of mechanical stress. Our mechano-chemostat is an easy-to-use microfluidic device that allows the long-term culture of biological samples and can be used to study both the impact of specific conditions as well as the consequences of mechanical compression.

biophysics↗

bioRxiv2020

Evolutionary Emergence of First Animal Organisms Triggered by Environmental Mechano-Biochemical Marine Stimulation

The evolutionary emergence of the first animals is thought to have been intimately associated to the formation of a primitive endomesodermal gut (i.e gastrulation) from ancestral multi-cellular spheres, blastulae, more than 700 million years ago. However, the biochemical cues having been at the origin of endomesoderm formation remain a mystery. Here we find that hydrodynamic mechanical strains developed by sea wavelets on pre-bilaterian Nematostella vectensis and pre-metazoan Choanoeca flexa representatives, which common ancestor dates back to more than 700 million years ago, can trigger gastrulation in a Myo-II dependent mechanotransductive process. Gastrulation in turn induces endomesoderm first biochemical specification through the mechanical activation of the {beta}cat pathway in pre-bilaterian Nematostella vectensis, like in Drosophila and zebrafish embryos, which common ancestor dates back to 600-700 million years ago. These observations converge to animal emergence that has been mechanotransductively triggered by wavelet mechanical strains on the sea-shore in multicellular choanoflagellates through Myo-II more than 700 million years ago, a process achieved in first metazoan through mechanosensitive Y654-containing {beta}cat evolutionary emergence found as conserved in all metazoan. One sentence summaryMarine hydrodynamic strains have activated first gastric organ formation from ancestral pre-animal cell colonies.

evolutionary biology↗