Force of change: How biomechanical cues drive endothelial plasticity and morphogenesis

Endothelial cells (ECs), which line the inner surface of blood vessels, continuously respond to biomechanical forces from blood flow, extracellular matrix, and intracellular tension. Recent advances have highlighted the pivotal role of these forces in regulating cellular plasticity during endothelial-to-hematopoietic transition (EHT) and endothelial-to-mesenchymal transition (EndMT), two processes essential for embryogenesis, tissue repair, and disease progression. EHT contributes to hematopoietic stem cell formation, and EndMT to valve formation and vessel sprouting. When misregulated, both processes cause vascular pathologies such as fibrosis, cancer metastasis, and atherosclerosis. This review provides an overview of how biomechanical cues influence EC fate decisions and behavioral transitions. We explore how external biomechanical forces are sensed at the endothelial cell surface, transmitted through intracellular adaptors, and affect changes at the transcriptional level. Understanding these mechanotransduction pathways during cell fate transition not only deepens our knowledge of endothelial cell plasticity but also provides insight into potential root causes of and treatments for vascular diseases.