Charged polymers modulate retrovirus transduction via membrane charge neutralization and virus aggregation
Charged polymers modulate retrovirus transduction via membrane charge neutralization and virus aggregation
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DOI：
10.1016/s0006-3495(04)74197-1
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发表时间：
2004-02-01
影响因子：
3.4
通讯作者：
Yarmush, ML
中科院分区：
文献类型：
--
作者：
Davis, HE;Rosinski, M;Yarmush, ML
通过表征带电聚合物对病毒转运和吸附的影响，分析了带电聚合物调控逆转录病毒转导的具体机制。从标准的胶体观点来看，两种机制，电荷屏蔽和病毒聚集，可以潜在地解释实验观察到的由于带电聚合物引起的吸附行为和生物物理参数的变化。实验测试表明，根据阳离子聚合物的特性，这两种机制都可能起作用。所有阳离子聚合物都通过电荷屏蔽增强了吸附和转导；然而，只有大于15 kDa的聚合物能够通过病毒聚集机制增强这些过程，解释了高分子量分子的更高效率增强。阴离子聚合物的作用也被表征，发现它们通过隔离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，这些发现为修订的病毒传输物理模型提供了基础，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。
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.