Laboratoire Matière et Systèmes Complexes

There will be a live diffusion with Zoom :

Monday January 16th, 11h30 in room 454 A.

Please contact Jean-Baptiste Manneville to attend the visio-seminar.

Microstructured surfaces for controlling cellular behavior : from understanding contact guidance to diagnosing diseases

Abdul Barakat

LadHyX , CNRS, Ecole Polytechnique, Institut Polytechnique de Paris

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 topographical cues on cell behavior in vitro. One such system that we have been using to elucidate the effect of surface topography on cellular structure and function is a substrate that consists of arrays of nano- to micro-scale grooves that are intended to mimic the anisotropic organization of the ECM.

We are particularly interested in vascular endothelial cells that line the inner surfaces of all blood vessels. In medium and large arteries, chronic endothelial inflammation is a trigger of atherosclerosis, the disease that leads to heart attacks and strokes. Interestingly, atherosclerotic lesions develop preferentially in arterial regions where endothelial cells are cuboidal and randomly oriented, whereas arterial zones that are characterized by highly elongated and aligned endothelial cells remain largely spared from the disease. Therefore, understanding the relationships between endothelial cell shape/alignment and function is of fundamental interest.

In this presentation, I will discuss four aspects of endothelial cell responsiveness to microgroove substrates. First, I will show how microgroove substrates can be used to noninvasively control endothelial cell shape and alignment and will describe our understanding of the mechanisms that underlie cell shape regulation by microgrooves. Second, I will describe dynamic live-cell recordings that demonstrate that microgrooves can orient the direction of migration of endothelial cells within monolayers and can lead to a unique pattern of collective cell migration that takes the form of antiparallel streams. Modeling the endothelial monolayer as an active fluid with the effect of the microgrooves considered as an energetic constraint on cell orientation predicts the occurrence of the antiparallel streams as well as their dimensions. Third, I will show how microgrooves lead to extensive deformation of endothelial cells and their nuclei and will evoke the interesting notion of using these deformations to diagnose certain diseases that involve abnormalities in cellular and nuclear mechanical properties. Finally, I will describe the competition between microgroove-derived contact stresses on the cells’ basal surface with flow forces on the cells’ apical surface and how this competition is a key determinant of endothelial cell shape and alignment.