NANOPHYSIOLOGY OF CELLS, CHANNELS AND NUCLEAR PORES - Life at the Nanoscale: Atomic Force Microscopy of Live Cells - page 133

cellular model describes this concept mainly based on AFM measurements
( Fig. 6.13 ) . The cortical cytoskeleton of vascular endothelial cells is highly
dynamic, and the state of polymerization of cortical actin determines the
structure and mechanical properties of this layer. 29,30 Monomeric globular
actin (G-actin) can rapidly polymerize into ilamentous actin (F-actin), which
causes a rapid change in local viscosity. The switch from F-actin to G-actin by
using the polymerization inhibitor cytochalasin D is associated with solation
of the cortex. 31 An increase in extracellular potassium mimics this response,
indicating that potassium per se softens the cortical actin cytoskeleton by
changing F-actin to G-actin. G-actin is known to colocalize with the endothelial
eNOS and to increase eNOS activity. 32,33 This could explain the activation of
eNOS by high potassium.
Sodium is possibly a functional antagonist in this system. Sodium
inlux increases the viscosity of the submembranous layer by stiffening
the cytoskeleton. When sodium is in the high physiological range, F-actin
dominates over monomeric actin. This explains the sodium-induced increase
in cell stiffness. When potassium is elevated, actin ilaments disaggregate
into actin monomers, and the endothelial cell softens. Both F-actin and G-
actin are negatively charged molecules, and the interaction with Na + and K +
will inally depend upon local concentrations and speciic afinities of the
respective ions. It has to be kept in mind that this scenario is supposed to
happen in a quite restricted cytosolic space, directly underneath the plasma
membrane, most likely at the caveolae. 34 Since this cytosolic submembranous
zone (cell shell) is only a few hundred nanometres thick, about 90% of the
cell body remains unchallenged.
Taken together, “local” mechanodynamics, i.e. the mechanical properties
underneath the plasma membrane, determines the function of vascular
endothelial cells.

6.3 NUCLEAR PORES

6.3.1 Apoptosis: Physiological Relevance of Apoptosis

For every cell, there is a time to live and a time to die, and cell death can be
executed by various injury types or by suicide. Unlike cell death by injury, the
process of cell death by suicide is highly orderly and is often referred to as
programmed cell death or apoptosis. Apoptosis is the regulated elimination
of cells that occurs naturally during the course of development, as well as in
many pathological circumstances that require cell death for the beneit of the
organism.