Biology subjects

Brunel, B.

Publications and source records attributed to Brunel, B..

3 recordsLinked to original sources

bioRxiv2025

Large extracellular vesicles subsets and contents discrimination: the potential of morpho mechanical approaches at single EV level

Extracellular vesicles (EVs) are heterogenous lipid bound membranous structures released by different cells, showing a great potential to be used as biomarkers. They have also been explored for their role in the context of environmental toxicity. When endothelial cells are exposed to pollutants like Polycyclic Aromatic Hydrocarbons (PAH) - the most common being benzo[a]pyrene (B[a]P) - EVs released from those cells undergo surface and cargo modifications. Subpopulations of large EVs (lEVs) have shown to contain either damaged or intact mitochondria which is inexorably linked to oxidative stress conditions. In this paper, we studied B[a]P induced modifications in lEVs derived from endothelial cells, through morpho mechanical characterization with atomic force microscopy (AFM). Colocalizing AFM with fluorescence microscopy allowed us to differentiate between EVs containing mitochondria and those that did not. EVs containing mitochondria had a larger size (maximum diameter) when coming from treated cells (1.8 {+/-} 0.89 {micro}m) as compared to control cells (1.63 {+/-} 0.76 {micro}m). Moreover, their Youngs moduli were higher in the treated condition (3.09 {+/-} 2.54 MPa in average) as compared to the control condition (1.25 {+/-} 0.92 MPa in average). We also observed a heterogeneity within single vesicles, with most Youngs modulus values ranging from 0.1 up to 30 MPa for the treated condition and from 0.1 to 5 MPa for the control condition. Finally, applying linear discriminant analysis (LDA) and Random Forest (RF) algorithms on maximum diameter, height, and distribution of Youngs modulus values, we demonstrated the possibility to discriminate between EV subpopulations. Indeed, we successfully managed to a) distinguish EVs containing mitochondria from the "empty" ones, with an accuracy of 84% and b) discriminate whether these mitochondria-containing EVs originated from control or treated conditions, with an accuracy of 76%. These findings highlight the power of combining morpho-mechanical analysis and machine learning for identifying and discriminating EV subpopulations, no longer requiring any EVs fluorescence labelling.

biophysics↗

bioRxiv2020

Extra-cellular Matrix in cell aggregates is a proxy to mechanically control cell proliferation and motility

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions. To perceive mechanical perturbations of different types and magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results of selective osmotic compressions of cells within multicellular aggregates with small osmolites and global aggregate compressions with big osmolites, we show that global compressions have a strong impact on the aggregates growth and internal cell motility, while selective compressions of same magnitude have almost no effect. Both compressions alter the volume of individual cells in the same way but, by draining the water out of the extracellular matrix, the global one imposes a residual compressive mechanical stress on the cells while the selective one does not. We conclude that, in aggregates, the extracellular matrix is as a sensor which mechanically regulates cell proliferation and migration in a 3D environment.

biophysics↗

bioRxiv2018

Extracellular Matrix acts as pressure detector in biological tissues

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions 1-5. To perceive mechanical perturbations of different types and magnitudes, tissues need a range of appropriate detectors 6-8, with a compliance that has to match the perturbation amplitude. As a proxy of biological tissues, we use multicellular aggregates, a composite material made of cells, extracellular matrix and permeating fluid. We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9-13, while the same amount of selective compression on cells has almost no effect 14,15. We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space. This description correctly predicts the emergent bulk modulus of the aggregate as well as the hydrodynamic diffusion coefficient of the percolating interstitial fluid under compression. We further show that, on a longer timescale, the extracellular matrix serves as a sensor that regulates cell proliferation and migration in a 3D environment through its permanent deformation and dehydration following the global compression.

biophysics↗