Under
deoxygenated conditions intermolecular
Hb S reactions initiate an intracellular deoxygenated-Hb S (deoxyHb
S) polymerization process. In vitro studies have shown that concentrated
solutions of deoxyHb S form a polymer gel or crystal [55].
Deoxygenated Hb S polymers are relatively insoluble in the cytosol[53].
Due to the non-ideality of protein, deoxyHb S in RBCs and in
solution behaves in a similar manner[54]. In concentrated solutions and within
intact RBCs, Hb S undergoes a deoxygenation-induced (polymer) gelation
process[54]. This deoxyHb
S polymerization process occurs via a
double nucleation mechanism[56]
involving two major steps: (1) formation of a critical nucleus, and (2)
formation of a 14-stranded Hb S fiber (or 7 “Wishner-Love” double strands,
each made up of Hb S polymers)[58].
The structure of deoxyHb S crystal and fibers has been investigated[57-61] and resolved down to atomic resolution[58-61] by two principal groups. First, using crystallography methods, Wishner and Love determined that Hb S polymers form double strands[58]. Then, using electron microscopy, Stuart Edelstein further determined that within a sickle polymer, 7 double-strands are arranged (with a characteristic helical twist) in one unit as a 14-strand Hb S fiber[61]. Minor discrepancies remain, however, between the two models of the Hb S fiber [55].