Heterogeneous Nucleation and Crowding in Sickle Hemoglobin: An Analytic Approach

Sickle hemoglobin nucleation occurs in solution as a homogeneous process or on existing polymers in a heterogeneous process. We have developed an analytic formulation to describe the solution crowding and large nonideality that affects the heterogeneous nucleation of sickle hemoglobin by using convex particle theory. The formulation successfully fits the concentration and temperature dependence of the heterogeneous nucleation process over 14 orders of magnitude. Unlike previous approaches, however, the new formulation can also accurately describe the effects of adding nonpolymerizing agents to the solution. Without additional adjustable parameters, the model now describes the data of M. Ivanova, R. Jasuja, S. Kwong, R. W. Briehl, and F. A. Ferrone, (Biophys. J. 2000, 79:1016–1022), in which up to 50% of the sickle hemoglobin is substituted by cross-linked hemoglobin A, which does not polymerize, and which substitution causes the rates to decrease by 105. The success of this approach provides insight into the polymerization process: from the size-dependence of the contact energy deduced here, it also appears that various contacts of unknown origin are energetically significant in the heterogeneous nucleation process.