KINETICS OF SICKLE HEMOGLOBIN POLYMERIZATION .2. A DOUBLE NUCLEATION MECHANISM
KINETICS OF SICKLE HEMOGLOBIN POLYMERIZATION .2. A DOUBLE NUCLEATION MECHANISM
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DOI：
10.1016/0022-2836(85)90175-5
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发表时间：
1985-01-01
影响因子：
5.6
通讯作者：
EATON, WA
中科院分区：
文献类型：
--
作者：
FERRONE, FA;HOFRICHTER, J;EATON, WA
描述了[人]镰状血红蛋白聚合的双重成核机制。该机制解释了所有主要的动力学观察结果：延迟的出现，延迟时间的高浓度依赖性，以及小体积缓慢聚合样品的随机行为。该机理假定聚合物的形成有2种途径：聚合是由溶液相中的均质成核引发的，然后是在现有聚合物的表面上的额外聚合物的成核。这第二个途径被称为异质成核。由于聚合物的表面随时间不断增加，异相成核提供了一种极端自催化的机制，表现为动力学进展曲线的明显延迟。在这种机制中，每个球晶域的聚合物被认为是由一个单一的均匀成核事件。该机制解释了单域形成的延迟时间的不可再现性，所产生的随机波动的时间，在该时间的均匀的核形成的第一聚合物。描述该模型的线性化速率方程的积分结果为简单的动力学形式：A[cosh（Bt）-1]。最初的10-15%的进度曲线，延迟时间从几毫秒到超过105秒不等，很好地符合这个方程。一个近似的统计热力学处理的平衡成核过程，显示了如何核的大小和成核平衡含量取决于单体浓度。平衡模型得到B和B2 A作为单体浓度的函数的表达式，其依据5个可调参数：单体向生长的聚集体的双分子加成速率，聚合单体中用作非均质成核位点的部分，聚合物内分子间键合的自由能，和2个描述自由能变化的参数，其作为异质核与聚合物表面键合的尺寸的函数。该模型使用物理上合理的参数提供了与作为浓度函数的B和B2 A的数据的极好拟合。该模型还正确地预测的时间制度，其中观察到的随机行为在小体积聚合。
A double nucleation mechanism for the polymerization of [human] sickle Hb is described. The mechanism accounts for all of the major kinetic observations: the appearance of a delay, the high concentration dependence of the delay time, and the stochastic behavior of slowly polymerizing samples in small volumes. The mechanism postulates that there are 2 pathways for polymer formation: polymerization is initiated by homogeneous nucleation in the solution phase, followed by nucleation of additional polymers on the surface of existing ones. This 2nd pathway is called heterogeneous nucleation. Since the surface of polymers is continuously increasing with time, heterogeneous nucleation provides a mechanism for the extreme autocatalysis that is manifested as an apparent delay in the kinetic progress curves. In this mechanism, each spherulitic domain of polymers is considered to be initiated by a single homogeneous nucleation event. The mechanism explains the irreproducibility of the delay time for single domain formation as arising from stochastic fluctuations in the time at which the homogeneous nucleus for the 1st polymer is formed. Integration of the linearized rate equations that describe this model results in a simple kinetic form: A[cosh(Bt)-1]. The initial 10-15% of progress curves, with delay times varying from a few milliseconds to over 105 s, is well fit by this equation. An approximate statistical thermodynamic treatment of the equilibrium nucleation processes is presented that shows how the nucleus sizes and nucleation equilibrium contents depend on monomer concentration. The equilibrium model results in expressions for B and B2A as a function of monomer concentration in terms of 5 adjustable parameters: the bimolecular addition rate of a monomer to the growing aggregate, the fraction of polymerized monomers that serve as heterogeneous nucleation sites, the free energy of intermolecular bonding within the polymer, and 2 parameters that describe the free energy change as a function of size for the bonding of the heterogeneous nucleus to a polymer surface. This model provides an excellent fit to the data for B and B2A as a function of concentration using physically reasonable parameters. The model also correctly predicts the time regime in which stochastic behavior is observed for polymerization in small volumes.