Davis Howard E, Rosinski Matthew, Morgan Jeffrey R, Yarmush Martin L
Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Biophys J. 2004 Feb;86(2):1234-42. doi: 10.1016/S0006-3495(04)74197-1.
The specific mechanisms of charged polymer modulation of retrovirus transduction were analyzed by characterizing their effects on virus transport and adsorption. From a standard colloidal perspective two mechanisms, charge shielding and virus aggregation, can potentially account for the experimentally observed changes in adsorption behavior and biophysical parameters due to charged polymers. Experimental testing revealed that both mechanisms could be at work depending on the characteristics of the cationic polymer. All cationic polymers enhanced adsorption and transduction via charge shielding; however, only polymers greater than 15 kDa in size were capable of enhancing these processes via the virus aggregation mechanism, explaining the higher efficiency enhancement of the high molecular weight molecules. The role of anionic polymers was also characterized and they were found to inhibit transduction via sequestration of cationic polymers, thereby preventing charge shielding and virus aggregation. Taken together, these findings suggest the basis for a revised physical model of virus transport that incorporates electrostatic interactions through both virus-cell repulsive and attractive interactions, as well as the aggregation state of the virus.
通过表征带电聚合物对病毒运输和吸附的影响，分析了其调节逆转录病毒转导的具体机制。从标准胶体角度来看，电荷屏蔽和病毒聚集这两种机制可能解释了实验观察到的由于带电聚合物导致的吸附行为和生物物理参数的变化。实验测试表明，这两种机制可能都在起作用，具体取决于阳离子聚合物的特性。所有阳离子聚合物都通过电荷屏蔽增强吸附和转导；然而，只有尺寸大于15 kDa的聚合物能够通过病毒聚集机制增强这些过程，这解释了高分子量分子更高的效率增强。还表征了阴离子聚合物的作用，发现它们通过螯合阳离子聚合物来抑制转导，从而防止电荷屏蔽和病毒聚集。综上所述，这些发现为病毒运输的修正物理模型奠定了基础，该模型通过病毒与细胞的排斥和吸引相互作用以及病毒的聚集状态纳入了静电相互作用。
