Biology subjects

Dessard, M.

Publications and source records attributed to Dessard, M..

3 recordsLinked to original sources

bioRxiv2025

AFM-based nanoscale characterization of physical interaction within hematopoietic stem cells niche at single-cell level

Hematopoietic stem cells (HSCs) produce all blood cells throughout the lifespan of the organism. HSC requires a specialized bone marrow microenvironment, known as the niche, for proper differentiation and self-renewal. While several molecular and cellular elements of the niche are described, the precise understanding of the mechanobiology underlying HSC adhesion to the niche remains poorly understood. Here, we aim to characterize physical interactions and adhesion within the hematopoietic niche by combining cell sorting, surface functionalization, and atomic force microscopy. Using this approach, we quantified and compared the adhesion of bone marrow (BM) mesenchymal stromal cells (MSCs) to different extracellular proteins, as well as the adhesion of HSCs to MSCs. We observed that MSCs adhere with the greatest force to fibronectin in an Arg-Gly-As (RGD) motif mediated and actin cytoskeleton-dependent manner. Additionally, we showed that HSCs strongly adhere to MSC within 30 seconds and that the binding is RGD-independent. In conclusion, we demonstrated how to implement atomic force microscopy to measure the physiological interactions within the HSCs niche in a direct, specific, and quantitative way. This approach provides a more comprehensive and precise characterization of the biology of the HSC niche compared to previously used methods. Furthermore, it highlights the complexity of studying extremely small structures and rare cell populations in biophysical experiments.

cell biology↗

bioRxiv2023

Dia2 formin controls receptor activity by organizing plasma membrane lipid partitioning at the nanoscale

Activation of JAK/STAT signaling by IFN-{gamma} requires partitioning of IFN-{gamma}R into specific lipid nanodomains at the plasma membrane. Using IFN-{gamma}R as a proxy, we investigated the role of actin dynamics in the formation and organization of lipid nanodomains, a process that remains poorly understood. We identified formin Dia2/DIAPH3 as a specific and RhoA -dependent regulator of IFN-{gamma}-induced JAK/STAT signaling. Based on lipidomics and specific probes enabling membrane lipid imaging by super resolution microscopy, we demonstrate that Dia2 is required for proper assembly of sphingomyelin and cholesterol lipid complexes. Finally, we show that the disorganization of lipid nanodomains induced by Dia2 depletion results in drastic changes in nano-partitioning and activity of other membrane proteins, such as Thy1 and PD-L1. Our data establish, therefore, the central role of the RhoA-Dia2 axis in the regulation of IFN-{gamma} induced JAK/STAT signaling, and more broadly, in the nanoscale organization of the plasma membrane.

cell biology↗

bioRxiv2023

Cytoplasmic Viscosity is a Potential Biomarker for Metastatic Breast Cancer Cells

AbstractCellular microrheology has shown that cancer cells with high metastatic potential are softer compared to non-tumorigenic normal cells. These findings rely on measuring the apparent Young modulus of whole cells using primarily atomic force microscopy. The present study aims to explore whether alternative mechanical parameters have discriminating features with regard to metastatic potential. Magnetic rotational spectroscopy (MRS) is employed in the examination of mammary epithelial cell lines: MCF-7 and MDA-MB-231, representing low and high metastatic potential, alongside normal-like MCF-10A cells. MRS utilizes active micron-sized magnetic wires in a rotating magnetic field to measure the viscosity and elastic modulus of the cytoplasm. All three cell lines display viscoelastic behavior, with cytoplasmic viscosities ranging from 10-70 Pa s and elastic moduli from 30-80 Pa. It is found that the tumorigenic MCF-7 and MDA-MB-231 cells are softer than the MCF-10A cells, with a twofold decrease in elastic modulus. To differentiate cells with low and high malignancy however, viscosity emerges as the more discriminating parameter, as MCF-7 exhibits a 5 times higher viscosity as compared to MDA-MB-231. These findings highlight the sensitivity of cytoplasmic viscosity to metastatic potential, suggesting its potential utility as a mechanical marker for malignant cancer cells. TOC Image O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/564072v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@16f5b87org.highwire.dtl.DTLVardef@1e2104aorg.highwire.dtl.DTLVardef@9babddorg.highwire.dtl.DTLVardef@306489_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗