J. Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Cracow, Poland.
J Colloid Interface Sci. 2012 Nov 1;385(1):244-57. doi: 10.1016/j.jcis.2012.07.010. Epub 2012 Jul 16.
Hydrodynamic properties of fibrinogen molecules were theoretically calculated. Their shape was approximated by the bead model, considering the presence of flexible side chains of various length and orientation relative to the main body of the molecule. Using the bead model, and the precise many-multipole method of solving the Stokes equations, the mobility coefficients for the fibrinogen molecule were calculated for arbitrary orientations of the arms whose length was varied between 12 and 18 nm. Orientation averaged hydrodynamic radii and intrinsic viscosities were also calculated by considering interactions between the side arms and the core of the fibrinogen molecule. Whereas the hydrodynamic radii changed little with the interaction magnitude, the intrinsic viscosity exhibited considerable variation from 30 to 60 for attractive and repulsive interactions, respectively. These theoretical results were used for the interpretation of experimental data derived from sedimentation and diffusion coefficient measurements as well as dynamic viscosity measurements. Optimum dimensions of the fibrinogen molecule derived in this way were the following: the contour length 84.7 nm, the side arm length 18 nm, and the total volume 470 nm(3), which gives 16% hydration (by volume). Our calculations enabled one to distinguish various conformational states of the fibrinogen molecule, especially the expanded conformation, prevailing for pH<4 and lower ionic strength, characterized by high intrinsic viscosity of 50 and the hydrodynamic radius of 10.6 nm. On the other hand, for the physiological condition, that is, pH=7.4 and the ionic strength of 0.15M NaCl, the semi-collapsed conformation dominates. It is characterized by the average angle equal to <φ>=55°, intrinsic viscosity of 35, and the hydrodynamic radius of 10nm. Additionally, the interaction energy between the arms and the body of the molecule was predicted to be -4 kT units, confirming that they are oppositely charged than the central nodule. Results obtained in our work confirm an essential role of the side chains responsible for a highly anisotropic charge distribution in the fibrinogen molecule. These finding can be exploited to explain anomalous adsorption of fibrinogen on various surfaces.
纤维蛋白原分子的流体动力学性质已通过理论计算得出。考虑到纤维蛋白原分子中各种长度和方向的柔性侧链的存在，将其形状近似为珠粒模型。使用珠粒模型和精确的多极子求解 Stokes 方程的方法，计算了纤维蛋白原分子在臂长为 12nm 至 18nm 之间变化的任意取向时的迁移率系数。通过考虑侧臂与纤维蛋白原分子核心之间的相互作用，还计算了取向平均流体力学半径和固有粘度。尽管流体力学半径随相互作用强度的变化很小，但固有粘度在吸引力和排斥力分别为 30 到 60 之间有很大的变化。这些理论结果用于解释从沉降和扩散系数测量以及动态粘度测量得出的实验数据。通过这种方式得出的纤维蛋白原分子的最佳尺寸如下：轮廓长度 84.7nm，侧臂长度 18nm，总体积 470nm(3)，这意味着 16%的水合度（按体积计）。我们的计算使人们能够区分纤维蛋白原分子的各种构象状态，特别是在 pH<4 和较低离子强度下占主导地位的扩展构象，其固有粘度为 50，流体力学半径为 10.6nm。另一方面，对于生理条件，即 pH=7.4 和 0.15M NaCl 离子强度，半折叠构象占主导地位。它的特征是平均角度等于 <φ>=55°，固有粘度为 35，流体力学半径为 10nm。此外，预测臂与分子主体之间的相互作用能为-4 kT 单位，证实它们带相反电荷比中央节结。我们工作中的结果证实了负责纤维蛋白原分子中高度各向异性电荷分布的侧链的重要作用。这些发现可用于解释纤维蛋白原在各种表面上的异常吸附。
