The effect of cell elongation and alignment via topographical micropatterning on the endothelial transcriptome

The aim of this study was to investigate the effect of endothelial cell (EC) elongation and alignment, independent of fluid shear stress (FSS), on the endothelial transcriptome. Endothelial cells are continuously exposed to a variety of biomechanical stimuli and must adapt their structure, gene expression, and phenotype to maintain vascular homeostasis. FSS-induced changes in EC morphology are highly associated with functional phenotype. However, to fully investigate EC mechanotransduction pathways, it is essential to decouple cell morphology from FSS. We, therefore, investigated the effects of elongated and aligned endothelial monolayers on the endothelial transcriptome. Baboon carotid artery endothelial cells (ECs) were seeded on either fully non-patterned, planar polyurethane culture substrates or micropatterned (3 µm wide anisotropic ridges and grooves, 1 µm depth) polyurethane culture substrates. We found EC elongation and alignment within static culture induced a highly differential gene transcriptome with a multitude of pro-inflammatory genes downregulated by ECs on micropatterned versus planar substrates. Collectively, our data support that endothelial morphology independently holds a critical role in the genetic transcriptome and may contribute to cardiovascular diseases and inflammation. To investigate cell elongation and alignment on the endothelial transcriptome, primary carotid artery endothelial cells isolated from a single male, juvenile baboon (Papio anubis) were cultured on either fully non-patterned or topographically micropatterned (3 µm wide ridges and grooves, 1 µm depth) polyurethane substrates. After 24 hours in static culture, endothelial cells were lysed