Morphological restriction of human coronary artery endothelial cells substantially impacts global gene expression patterns

Abstract

Alterations in cell shape have been shown to modulate chromatin condensation and cell lineage specification; however, the mechanisms controlling these processes are largely unknown. Because endothelial cells experience cyclic mechanical changes from blood flow during normal physiological processes and disrupted mechanical changes as a result of abnormal blood flow, cell shape deformation and loss of polarization during coronary artery disease, we aimed to determine how morphological restriction affects global gene expression patterns. Human coronary artery endothelial cells (HCAECs) were cultured on spatially defined adhesive micropatterns, forcing them to conform to unique cellular morphologies differing in cellular polarization and angularity. We utilized pattern recognition algorithms and statistical analysis to validate the cytoskeletal pattern reproducibility and uniqueness of each micropattern, and performed microarray analysis on normal-shaped and micropatterned HCAECs to determine how constrained cellular morphology affects gene expression patterns. Analysis of the data revealed that forcing HCAECs to conform to geometrically-defined shapes significantly affects their global transcription patterns compared to nonrestricted shapes. Interestingly, gene expression patterns were altered in response to morphological restriction in general, although they were consistent regardless of the particular shape the cells conformed to. These data suggest that the ability of HCAECs to spread, although not necessarily their particular morphology, dictates their genomics patterns. Alterations in cell shape affect endothelial cell function, yet it is unknown how morphological restriction affects the transcriptome. We cultured endothelial cells on spatially defined adhesive micropatterns and used pattern recognition algorithms, statistical analysis, and microarray data to demonstrate that the ability of endothelial cells to spread, but not necessarily their particular morphology, dictates their global gene expression patterns. © 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.