Crystallization of sickle hemoglobin from gently agitated solutions—An alternative to gelation

A new, crystalline state of deoxygenated sickle hemoglobin is described which is formed spontaneously in agitated concentrated hemoglobin S solutions under conditions otherwise favoring the well-known transition to the gel state. The birefringent, needle-like sickle hemoglobin crystals, which may subsequently grow to exceed 1 mm in length, are completely dissolved upon dropping the temperature to 0°C. Gelation can thereafter be induced by raising the temperature again without agitating the solution. It is shown by means of solubility and crystal-seeding experiments that hemoglobin S gels are thermodynamically unstable with respect to the crystalline form near the physiological values of pH and ionic strength. The rigid Hb S‡ gel is slowly transformed into a free-flowing crystal suspension after being “seeded” with a minute amount of crystalline sickle hemoglobin. The kinetics of crystallization, as a function of concentration and temperature, together with the enthalpy of crystallization, are compared with the corresponding quantities for gelation.