Biomedical Engineering Reference
In-Depth Information
Red blood capsules undergo tumbling, swinging, tank-treading, and deformation
in the microvasculature.
30
Tumbling-to-tank-treading transition, and not capsule
deformation (i.e., stretching), contributes to the shear-thinning behavior (Vol. 7 -
Chap. 5. Rheology) [
126
]. However, RBC deformation intervenes in ATP release,
but not the transition from tumbling to tank-treading.
Both deformation-dependent and -independent ATP export occur through
pannexin-1 hemichannel. Liberation of ATP through pannexin-1 mainly remains
constant at shear stresses below a threshold (3 Pa), i.e., when RBC begins to
deform [
126
]. Above this threshold, large RBC deformations occur and ATP release
increases. Cystic fibrosis transmembrane conductance regulator contributes to
deformation-dependent ATP release above the mechanical stress threshold. Large
changes in local membrane curvature can dissociate spectrin from actin, thereby
reducing the cell shear modulus and enabling actin binding to CFTR, hence its
activation [
127
].
3.5.4
Influence of Oxygen Content in the Local Environment
Human RBCs circulate between lungs and tissues approximately every minute.
In the lung, where O
2
partial pressure is high, RBCs are exposed to oxidative
stresses that must be controlled by accelerated production of reducing equivalents
derived from the pentose phosphate pathway [
128
]. In tissues, where O
2
partial
pressure is low, deformed RBCs in capillaries undergo mechanical stresses that
induce cation leaks. This leak and deoxygenation elevates glycolysis to produce
ATP and restore intracellular ion balances and represses pentose phosphate pathway
in RBCs.
Erythrocyte metabolism is regulated via the oxygen-dependent assembly of
glycolytic enzymes into inhibitory complexes bound to the membrane anion
transport SLC4a1 protein. In vivo, SLC4a1 acts as an oxygen-dependent metabolic
regulator because it interacts with deoxyhemoglobin with high affinity, but not
oxyhemoglobin [
128
]. Deoxyhemoglobin targets the same binding site on SLC4a1
as glycolytic enzymes. Therefore, upon deoxygenation, glycolytic enzymes are
released and promote glycolysis. On the other hand, in oxygenated RBCs, glycolytic
enzymes are inhibited, as they connect to SLC4a1 carrier.
bound C-peptide is involved in the breakdown of insulin hexamer. In blood, C-peptide interacts
with RBC when it is linked to a metallic ion (e.g., Zn
2
+
and Fe
2
+
)[
122
].
30
Tumbling is an end-over-end rigid body rotation. Tank-treading is the rotation of the cell
membrane around the center of mass of the cell [
123
,
124
]. Swinging is an oscillatory movement
of the cell's inclination angle during tank-treading, with a period and an amplitude that increases
with decreasing shear rates [
125
]. Stretching by large shear rates is an extension of the long cell
axis with shape changes from an oblate to a prolate ellipsoid, without variation of the membrane
surface area. Tank-treading and tumbling depend on the viscosity ratio (ratio of cytosol viscosity
to suspending solution viscosity) and membrane elasticity.
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