Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 566

The endothelial membrane is the first wall component to bear stresses from
circulating blood. 152 The bulk cell content can be supposed to be a fluid-like ma-
terial that contains solid particles and a cytoskeleton, wrapped into a solid-like
membrane. 153 Membrane tension has been estimated to be 3 orders of magnitude
higher than wall shear stress imposed by the flowing blood [ 1050 ]. Membrane
tension is affected by transmembrane static and osmotic pressures. It also at least
partially controls osmotic pressures. Membrane tension influences not only the
cytosol 154 and nucleus configurations by stress transmission, the cytoskeleton being
moored to anchoring membrane proteins, but also the mass transport across the cell
membrane, via pores, channels, or vesicles, and, thus, cell metabolism. Interactions
thus occur between cell internal structures and messengers using electrochemical
and biochemical processes.
Mechanical stresses alter structure and function at both cellular and molecular
levels. Stresses can directly act on stretch-activated channels (SAC), which are
sensitive to tension imposed on cell membrane [ 1051 ]. 155 Mechanosensitive ion
channels can indeed be opened by membrane stretch. They convert external
mechanical forces into electrochemical signals in the cell.
Mechanical stresses act not only on molecular transport from flowing blood
to the endothelial surface, but also on transendothelial transfer and through the
wall directly by interface deformation. Mechanical stresses cause conformational
changes of membrane proteins (ion channels, adhesion molecules, etc.), of pro-
teins associated with membrane proteins, and/or of proteins associated with the
cytoskeleton.
Because arteries convey pulsatile flows, arterial walls are subjected to tension,
with steady and time-dependent components. High steady intraluminal pressures
( 20 kPa) activate focal adhesion kinases. Phosphorylated FAK binds to GRB2

adaptor and stimulate a pathway that involves extracellular signal-regulated kinase-
1 and -2, Src kinase, and integrins [ 1053 ]. However, FAK is not implicated in cyclic
stretches, although ERK1 and ERK2 are activated.

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152 The membrane can be subdivided into 3 parts according to its neighborhood. A luminal part,
which is subjected to the wall shear stress, has a protruding segment above the average cell height
due to the nucleus. The nucleus in the stress field bears deformation; it is elongated, like the whole
cell, in the streamwise direction. The abluminal part, which adheres to BM, and sides, which have
a given inclination and are connected to adjoining endothelial membranes, are subjected to wall
tension imposed by the blood pressure and transmitted by the extracellular matrix and adjacent
endothelial cells.
153 The plasma membrane of endothelial cells can be assumed to be a solid-like material because it
resists applied stresses by deformation and not by flow.
154 The configuration of the marginal fiber network may be imposed by the direction of principal
stresses undergone by the membrane to which it adheres.
155 Other stretch-sensitive ion channels are implicated in mechanotransduction and osmoregulation.
They include stretch-inactivated K + channels, which can be detected in neurons [ 1052 ].