Using microstructured substrates to control cellular behavior: contact guidance of vascular endothelial cells on microgrooves

Adherent cells in vivo often reside on extracellular matrices (ECMs) that possess a topographical organization at different scales. Various types of engineered microstructured substrates have been developed to study the impact of basal topographical cues on cell behavior in vitro. Amongst them, microgrooves mimicking the anisotropic organization of the ECM have been shown to align and elongate different cell types. However, how cells detect and respond to microgrooves remains unclear, particularly for cellular monolayers. We are investigating these questions using vascular endothelial cells (ECs), which form a monolayer lining the inner surfaces of blood vessels, as a model.

In the first part of this presentation, I will focus on the collective migration of vascular endothelial cell monolayers on microgrooved substrates. We describe the emergence of a specific pattern of collective motion characterized by large antiparallel cell streams, which can be predicted in the physical framework of active fluids. I will then address the cellular and subcellular mechanisms underlying the contact guidance response of vascular endothelial cells on the microgrooves. We have in particular highlighted distinct regimes and mechanisms of response to topography in single cells vs. monolayers. Finally, I will present some preliminary results on the deformation of cell nuclei on microgrooved substrates. We have characterized the cellular mechanisms leading to nuclear deformations in the grooves and investigated the links between nuclear deformations and mechanics. We believe that microgrooves constitute a new, simple and high-throughput system to study cell and nuclear mechanics in physiological and/or pathological settings.