Biomedical Engineering Reference
In-Depth Information
Chapter 6
on Single Cell Motility
6.1 Biological Introduction
Finely tuned spatiotemporal calcium events are a highly conserved and ubiq-
uitous mode for the control of biochemistry and physiology in almost all eu-
karyotic cells [35, 40, 86]. Endothelial cells (ECs) are no exception, and intra-
cellular calcium serves as a positive or negative regulatory signal for a wide
range of cell functions, including survival, proliferation, motility, apoptosis,
and differentiation [34, 36, 276]. A broad number of calcium-dependent en-
zymes are also associated with the progression through the cell cycle (the exit
from quiescence in early G1 phase, the G1/S transition and other checkpoints
during S and M phases [22, 204, 280]), and mediate the activation of several
nuclear factors involved in the DNA division machinery, for example cdk and
cyclins [108, 130, 340].
Under resting conditions, different control mechanisms maintain the con-
centration of free cytosolic calcium very low, nearly 10
7
M, with respect to
the extracellular environment and to intracellular compartments (primarily
the endoplasmic reticulum, ER [7, 330, 372]). In particular, the ion is extruded
from the cytosol by calcium pumps, which are present in both plasma and ER
membranes (respectively, PMCAs and SERCAs) and directly consume ATP
energy, and by Na-Ca exchangers, which are located only in the plasmamem-
brane and use the energy of Na
+
electrochemical gradients [166, 191, 399]. On
the other hand, calcium enters into the cytosol through permeable channels
sited within the different membranes and activated by intracellular messengers
[33, 292].
The correct Ca
2+
concentration is thus strictly regulated by these active
and passive fluxes. Alterations of this fine balance can be triggered only by
specific extracellular agonists, and are typical chemical signals transducing
information during specific phases of vascular progression in both physiolog-
ical (such as vascularization of ovary and uterus during the menstrual cycle,
of mammary glands during lactation and of granulation tissue after wound
healing) and pathological (for example, chronic inflammatory diseases, vascu-
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