Mechanotransduction in endothelial cell migration

Abstract

The migration of endothelial cells (ECs) plays an important role in vascular remodeling and regeneration. EC migration can be regulated by different mechanisms such as chemotaxis, haptotaxis, and mechanotaxis. This review will focus on fluid shear stress-induced mechanotransduction during EC migration. EC migration and mechanotransduction can be modulated by cytoskeleton, cell surface receptors such as integrins and proteoglycans, the chemical and physical properties of extracellular matrix (ECM) and cell-cell adhesions. The shear stress applied on the luminal surface of ECs can be sensed by cell membrane and associated receptor and transmitted throughout the cell to cell-ECM adhesions and cell-cell adhesions. As a result, shear stress induces directional migration of ECs by promoting lamellipodial protrusion and the formation of focal adhesions (FAs) at the front in the flow direction and the disassembly of FAs at the rear. Persistent EC migration in the flow direction can be driven by polarized activation of signaling molecules and the positive feedback loops constituted by Rho GTPases, cytoskeleton, and FAs at the leading edge. Furthermore, shear stressinduced EC migration can overcome the haptotaxis of ECs. Given the hemodynamic environment of the vascular system, mechanotransduction during EC migration has a significant impact on vascular development, angiogenesis, and vascular wound healing.

Integrating biological vasculature into a multi-organ-chip microsystem

“…We have generated first indications that once a microvascular circulation system is established, it eventually has an operating life of at least 32 days. The unique combination of realtime video microscopy, live cell imaging and mPIV at one and the same location of the microvascular circulation system makes it a perfect tool for the basic investigation of all aspects of EC migration described, 61 such as chemotaxis, duro-or mechanotaxis, 62 haptotaxis, 63 or a combination of these cues. 64 This EC motility, as outlined by Young and co-workers, is critical to fundamental biology, pathology and tissue repair with the prime focus on understanding vasculogenic and angiogenic processes.…”

Effects of hypergravity on the angiogenic potential of endothelial cells

“…Endothelial cells (ECs), which constitute the inner layer of blood vessels (the endothelium), are biomechanically responsive cells, given that their phenotype and function are continuously conditioned by local haemodynamics (fluid shear stress, pressure and associated stretch) [2]. Mechanical forces acting on ECs are responsible for regulating angiogenic and inflammatory responses [3,4]. Angiogenesis is the process of blood vessel formation from pre-existing ones, playing a crucial role throughout postnatal life in physiological (e.g.…”

Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium

“…510 HMEC-1 were also challenged under hypoxic conditions for their ability to migrate, invade 511 the ECM and form tube-like structures. Indeed, ECM structure and composition provides a 512 scaffold and signals for cell adhesion and migration during tissue restoration [Li et al, 2005]. 513 ECM effect on angiogenesis appears highly variable over time, strictly depending on protein 514 constituents, protease actions, and ECM ability to sequester growth factors and bioactive 515 molecular fragments [Wells et al, 2015].…”