Kinetics of hemoglobin S polymerization and gelation under shear: I. Shape
of the viscosity progress curve and dependence of delay time and reaction
rate on shear rate and temperature
RW Briehl and P Nikolopoulou
Department of Physiology & Biophysics, Albert Einstein College of
Medicine, Bronx, NY 10461.
Polymerization and gelation of deoxyhemoglobin S makes red blood cells
(RBCs) rigid and is the immediate basis of pathogenesis in sickle cell
disease. Hence, characterization of hemoglobin S viscosity and its time-
dependent development as RBCs pass through the microvasculature is
important in understanding pathogenesis. Because RBCs and the
intraerythrocytic milieu in vivo are subject to shear, the shear dependence
of polymerization kinetics is also important. In steady- state cone-plate
viscometry we find: (1) gelation under shear progresses exponentially with
time; (2) shear markedly increases exponential rate and (3) shortens delay
time independent of when in the delay time it is applied; (4) shear greatly
decreases the temperature dependence of the exponential rate and delay
time; (5) simultaneous with its acceleratory effect on polymerization,
shear breaks down gel structure. We conclude that shear acts to accelerate
gelation by breaking fibers and creating new growing ends, a process that
occurs in addition to the homogeneous and heterogeneous nucleation of new
fibers that occurs in the absence of shear. Fibers that break are part of a
gel network rather than in free solution. The shear dependence of gelation
rates means that the critical clinical issue, whether the delay time is
long enough and gelation slow enough to permit deoxygenated cells to pass
through the microvasculature before they rigidify, depends on in vivo shear
rates as well as on degree of unsaturation and hemoglobin concentration.
Volume 81,
Issue 9,
pp. 2420-2428,
05/01/1993
Copyright © 1993 by The American Society of Hematology
