Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 563

9.10 Chemical and Mechanical Regulation

of the Vasomotor Tone

Any cell acts on its environment and vice versa. Mechanical forces, such as
forces applied by adjoining cells or the surrounding matrix, as well as forces
developed by a given cell on its matrix or contacting cells, are transmitted. The soft
extracellular matrix contains a three-dimensional fibrous mesh that sends and
receives mechanical stimuli.
Living cells not only sense applied forces and respond to received signals, but
also evaluate mechanical properties of their matrix, in particular the stiffness of the
extracellular matrix. 147 Moreover, the cell can recognize a local membrane curva-
ture and recruit small GTPases to the curved parts of the plasma membrane [ 1044 ].
Fiber curvature can induce cell-membrane curvature. Besides, certain K + channels
are opened by a convex curvature of the membrane.
Furthermore, endothelial cells have a wetted surface that faces flow forces.
Blood vessel walls are permanently subjected to tension and shear. In endothelial
cells, hemodynamic stress applied on the wetted apical surface produces fast
remodeling of mechanical stress-responsive focal adhesions that orient in the
streamwise direction at basal cell sites where resulting stress of transmitted forces
concentrates [ 1045 ]. Moreover, increase in focal adhesion size and decrease in
number result from coalescence of small adhesion sites. Focal adhesion remodeling
is accompanied by redistribution of stress fibers.
Mechanotransduction starts with mechanosensing and leads to a relatively quick
mechanoresponse. Molecular sensing of forces is transduced into biochemical
signals that drive cell responses to properly shape cells and tissues and trigger
suitable cell functions. The force can act not only by its magnitude and direction
but also by the loading rate.
Mechanical forces regulate cell function so that the vessel wall restores basal
stress conditions (Fig. 9.7 ). The cell changes its shape and adapts to the mechanical
loading. The cytoskeleton of mural cells transmits and modulates stresses within the
cell via cellular junctions and cell-matrix adhesion sites. Moreover, applied forces
initiate mechanotransduction cascades leading to transcription factor activation and
subsequent gene expression.
Mechanosensing occurs locally at the plasma membrane. It can be done by
conformational changes in plasmalemmal proteins and can involve cytoskeletal
filaments that propagate loadings down to the nucleus. 148 Force sensing can be
processed by: (1) partial protein unfolding with gain or loss of binding sites or of
enzyme function; (2) opening of mechanosensitive ion channels due to membrane
tension or to stress applied by force-bearing filaments connected to channels; and
(3) strained receptor-ligand interactions [ 1044 ].

147 Different cell types respond differently to matrix rigidity.
148 Cytoskeletal early responses take seconds to minutes.