Tightening the barrier: mechanical forces and the control of endothelial permeability

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...

Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation.

The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last for...

Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...