Biology subjects

Marchand, M. F.

Publications and source records attributed to Marchand, M. F..

3 recordsLinked to original sources

bioRxiv2025

Adaptation of endothelial cells to microenvironment topographical cues through lysyl oxidase like-2-mediated basement membrane scaffolding

Basement membrane (BM) provides structural support and signaling platform for blood vessels. While its major structural components are required for vascular morphogenesis, integrating BM regulators, like the lysyl oxidase LOXL2, and BM assembly in cell response to microenvironement cues remain poorly understood. Here we study the early deposition and supramolecular assembly of BM components using correlative atomic force and fluorescence microscopy. The fibrillar deposition of fibronectin is gradually remodeled and associates with the collagen IV meshwork as it organizes into BM. We demonstrate that LOXL2 is deposited with both proteins and participates in their remodeling. Alteration of BM scaffolding by LOXL2-depletion affects focal adhesion maturation and cytoskeleton remodeling. This altered BM organization maintains stress fibers, affects the distribution and activation of mechanosensors and alters cell barrier properties. Furthermore, using 3D micro-printed substrates, we demonstrate that BM assembly regulates endothelial cell response to topographical constraint. We therefore propose a mechanism directly linking the scaffolding of BM components and adaptation to the topographical signals from the microenvironment.

cell biology↗

bioRxiv2025

Extracellular matrix deposition controls early differentiation patterns in human cardiac gastruloids

Amongst the various factors that affect differentiation and tissue organization, the autonomous deposition of extracellular matrix (ECM) has hardly been considered in the context of gastruloids. Using biofunctionalized colloidal particles as artificial organizing centers (aOCs), we patterned differentiation loci within 3D embryonic bodies. Our findings reveal that the spatial distribution of the aOCs induces various pattern organizations, mediated by endogenous deposition of ECM. We investigated how the interplay between meso-endoderm cell epithelial-to-mesenchymal transition, migration into germ layers, and the prolonged maintenance of local stem-cell niches orchestrates gastruloid structure and composition. These factors collectively regulate the complexity of emergent cardiac structures observed at later time points. This work uncovers a critical feedback loop between cell differentiation rates and endogenous ECM deposition patterns, which governs the differentiation paths in scaffolded cardiac gastruloids.

cell biology↗

bioRxiv2022

Topology of connective tissues: a key parameter in cellular heterogeneity, beyond composition and stiffness

Cellular plasticity is essential in physiological contexts, including pathological ones. It is the basis of morphogenesis and organogenesis, as well as tumorigenesis and metastasis. The extracellular matrix (ECM) is a key player in the generation of cellular heterogeneity. Advances in our understanding of cell plasticity rely on our ability to provide relevant in vitro models. This requires to catch the characteristics of the tissues that are essential for controlling cell fate. To do this, we must consider the diversity of tissues, the diversity of physiological contexts, and the constant remodeling of ECM along these processes. To this aim, we have fabricated a library of ECM models for reproducing the scaffold of connective tissues and basement membrane with different biofabrication routes based on the electrospining and drop casting of biopolymers. Using a combination of multiphoton imaging and nanoindentation, we show that we can vary independently protein composition, topology of connective tissues and stiffness of ECM models. Reproducing the features of a tissue and physiological context in turns allows to generate the complexity of the phenotypic landscape associated with the epithelial-to-mesenchymal transition (EMT) in human ovarian cancer. We show that EMT shift cannot be directly correlated with a unique ECM feature, which reflects the multidimensionality of living environments. Very importantly, our combinatorial approach allows us to provide in vitro models, where the impact of the topological cues on cellular phenotypes can be revealed, beyond protein composition and stiffness of the ECM matrix. On this line, this work is a further step towards the development of ECM models recapitulating the constantly remodeled scaffolding environment that cells face and provides new insights for the development of cell-free matrices.

bioengineering↗