Zhang Qiufen, Bai Qingwen, Zhu Lin, Hou Tianhao, Zhao Jiang, Liang Dehai
Beijing National Laboratory for Molecular Sciences, Department of Polymer Science and Engineering and the Key Laboratory of Polymer Chemistry and Physics of the Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
ACS Appl Bio Mater. 2020 Jan 21;3(1):412-420. doi: 10.1021/acsabm.9b00892. Epub 2020 Jan 7.
The dense medium modulates the molecular structure and bioreactions in living cells via both noncovalent interactions and macromolecular crowding and confinement effects. However, the interplay between the volume effect and noncovalent interactions remains unclear. In this work, we studied in detail on how electrostatic interactions influence the crowding and confinement effect by comparing the formation and elongation of DNA nanotubes in branched dextran and charged hyaluronic acid (HA) solution of a broad concentration range, with and without 150 mM NaCl. In all the studied cases, three concentration regimes are identified: a crowding regime, a double-effect regime, and a confinement regime. In the crowding and double-effect regimes, the addition of 150 mM NaCl enhances the assembly of DNA tiles by screening the electrostatic repulsion, and a higher dextran solution is required to confine the DNA assembly into nanotubes. However, the screening effect on the HA network is more than that on the DNA assembly, so DNA tubes formed in HA solution at much lower concentrations. In the confinement regime, the electrostatic interaction exhibits a negligible effect on the DNA assembly in both dextran medium and HA medium. Our study demonstrates that the volume effect and noncovalent interactions are system specific and concentration dependent. Their interplay governs the living processes in crowded cells.
致密介质通过非共价相互作用以及大分子拥挤和限制效应来调节活细胞中的分子结构和生物反应。然而，体积效应与非共价相互作用之间的相互作用仍不清楚。在这项工作中，我们通过比较在有无150 mM NaCl的情况下，在宽浓度范围的支链葡聚糖和带电透明质酸（HA）溶液中DNA纳米管的形成和伸长情况，详细研究了静电相互作用如何影响拥挤和限制效应。在所有研究的情况下，确定了三种浓度范围：拥挤范围、双效应范围和限制范围。在拥挤和双效应范围内，添加150 mM NaCl通过屏蔽静电排斥增强了DNA瓦片的组装，并且需要更高浓度的葡聚糖溶液来将DNA组装限制成纳米管。然而，对HA网络的屏蔽效应比对DNA组装的屏蔽效应更大，因此在HA溶液中以低得多的浓度形成DNA管。在限制范围内，静电相互作用对葡聚糖介质和HA介质中的DNA组装均显示出可忽略不计的影响。我们的研究表明，体积效应和非共价相互作用是系统特异性的且依赖于浓度。它们的相互作用支配着拥挤细胞中的生命过程。
