Zhang X, Wang J-C, Lacki K M, Liapis A I
Department of Chemical and Biological Engineering and Biochemical Processing Institute, University of Missouri-Rolla, Rolla, MO 65409-1230, USA.
J Phys Chem B. 2005 Nov 10;109(44):21028-39. doi: 10.1021/jp053421h.
Significant increases in the separation of bioactive molecules by using ion-exchange chromatography are realized by utilizing porous adsorbent particles in which the affinity group/ligand is linked to the base matrix of the porous particle via a polymeric extender. To study and understand the behavior of such systems, the M3B model is modified and used in molecular dynamics (MD) simulation studies to construct porous dextran layers on the surface of a base matrix, where the dextran polymer chains and the surface are covered by water. Two different porous polymer layers having 25 and 40 monomers per main polymer chain of dextran, respectively, are constructed, and their three-dimensional (3D) porous structures are characterized with respect to porosity, pore size distribution, and number of conducting pathways along the direction of net transport. It is found that the more desirable practical implications with respect to structural properties exhibited by the porous polymer layer having 40 monomers per main polymer chain, are mainly due to the higher flexibility of the polymer chains of this system, especially in the upper region of the porous structure. The characterization and analysis of the porous structures have suggested a useful definition for the physical meaning and implications of the pore connectivity of a real porous medium that is significantly different than the artificial physical meaning associated with the pore connectivity parameter employed in pore network models and whose physical limitations are discussed; furthermore, the methodology developed for the characterization of the three-dimensional structures of real porous media could be used to analyze the experimental data obtained from high-resolution noninvasive three-dimensional methods like high-resolution optical microscopy. The MD modeling and simulations methodology presented here could be used, considering that the type and size of affinity group/ligand as well as the size of the biomolecule to be adsorbed onto the affinity group/ligand are known, to construct different porous dextran layers by varying the length of the polymeric chain of dextran, the number of attachment points to the base matrix, the degree of side branching, and the number of main polymeric chains immobilized per unit surface area of base matrix. After the characterization of the porous structures of the different porous dextran layers is performed, then only a few promising structures would be selected for studying the immobilization of adsorption sites on the pore surfaces and the subsequent adsorption of the bioactive molecules onto the immobilized affinity groups/ligands.
通过使用离子交换色谱法显著提高生物活性分子的分离效果，这是通过利用多孔吸附剂颗粒实现的，其中亲和基团/配体通过聚合物延伸剂与多孔颗粒的基体相连。为了研究和理解此类系统的行为，对M3B模型进行了修改，并用于分子动力学（MD）模拟研究，以在基体表面构建多孔葡聚糖层，其中葡聚糖聚合物链和表面被水覆盖。分别构建了两种不同的多孔聚合物层，葡聚糖每条主聚合物链分别具有25个和40个单体，并对其三维（3D）多孔结构在孔隙率、孔径分布以及沿净传输方向的传导路径数量方面进行了表征。研究发现，每条主聚合物链具有40个单体的多孔聚合物层在结构特性方面表现出更理想的实际意义，这主要归因于该系统聚合物链具有更高的柔韧性，尤其是在多孔结构的上部区域。对多孔结构的表征和分析为真实多孔介质的孔隙连通性的物理意义和影响提出了一个有用的定义，该定义与孔隙网络模型中使用的孔隙连通性参数所关联的人工物理意义有显著不同，并讨论了其物理局限性；此外，所开发的用于表征真实多孔介质三维结构的方法可用于分析从高分辨率无创三维方法（如高分辨率光学显微镜）获得的实验数据。考虑到亲和基团/配体的类型和大小以及要吸附到亲和基团/配体上的生物分子的大小已知，此处介绍的MD建模和模拟方法可用于通过改变葡聚糖聚合物链的长度、与基体的连接点数、侧支化程度以及每单位基体表面积固定的主聚合物链数来构建不同的多孔葡聚糖层。在对不同多孔葡聚糖层的多孔结构进行表征之后，然后仅选择少数有前景的结构来研究吸附位点在孔表面的固定以及随后生物活性分子在固定的亲和基团/配体上的吸附。
