| Popis: |
Red cell rigidification and damage due to polymerization and gelation of deoxygenated sickle cell hemoglobin lie at the root of pathogenesis in sickle cell disease. Although the abnormal blood rheology and gel viscosity have been studied, viscoelasticity has been little examined. Using sensitive cone-plate dynamic rheometry at low shear, we followed development of gels kinetically over 5 decades of increasing elasticity, G′ and loss modulus, G", until final levels were reached. Viscoelasticity progresses through 3 regimes. (1) A rapid, brief increase in G′ and G″ that occurs after initial nucleation can be explained as an initial quadratic dependence on time predicted to result from linear progress of both initiating nucleation and fiber growth with time. The percolation transition from fluid to solid viscoelasticity may also contribute to early rheological change. (2) Following stage (1), G′ and G″ increase exponentially, consistent with the dominance of heterogeneous nucleation of new fibers on the existing fiber mass. Exponential rates, B=dlnG/dt, scale as the approximate 100th power of solution hemoglobin concentration. The increasing viscoelasticity depends on polymer density, known to increase exponentially, but is also affected by two patterns of interfiber cross-linking and by domain size, packing, overlap and interdigitation. (3) Viscoelasticity reaches asymptotic levels. Final levels of G′ and G″ have a low, between linear and quadratic, power dependence on gel density. At 15 mM(heme), about 3/4 the normal red cell concentration, G′.150 KPa. This three stage sequence shows more complexity for concentrations near 14 mM heme, with changes in exponential rate during stage (2): slow exponential progress is followed by reacceleration. The slow, near-plateau, regime may depend on entanglements in a rubber-like polymeric system, but with the addition of continuing polymerization that causes residual increase in the plateau modulus, Ge. |
