DWI-Leibniz Institute for Interactive Materials e.V. , Forckenbeckstraße 50 , 52074 Aachen , Germany.
Functional and Interactive Polymers, Institute of Technical and Macromolecular Chemistry, RWTH Aachen University , Forckenbeckstraße 50 , 52074 Aachen , Germany.
Biomacromolecules. 2019 Apr 8;20(4):1578-1591. doi: 10.1021/acs.biomac.8b01775. Epub 2019 Mar 18.
A striking discovery in our work is that the distribution of ionizable groups in polyampholyte microgels (random and core-shell) controls the interactions with the captured proteins. Polyampholyte microgels are capable to switch reversibly their charges from positive to negative depending on pH. In this work, we synthesized differently structured polyampholyte microgels with controlled amounts and different distribution of acidic and basic moieties as colloidal carriers to study the loading and release of the model protein cytochrome c (cyt-c). Polyampholyte microgels were first loaded with cyt-c using the electrostatic attraction under pH 8 when the microgels were oppositely charged with respect to the protein. Then the protein release was investigated under different pH (3, 6, and 8) both with experimental methods and molecular dynamics simulations. For microgels with a random distribution of ionizable groups complete and accelerated (compared to polyelectrolyte counterpart) release of cyt-c was observed due to electrostatic repulsive interactions. For core-shell structured microgels with defined ionizable groups, it was possible to entrap the protein inside the neutral core through the formation of a positively charged shell, which acts as an electrostatic potential barrier. We postulate that this discovery allows the design of functional colloidal carriers with programmed release kinetics for applications in drug delivery, catalysis, and biomaterials.
我们的研究工作中一个显著的发现是，聚两性电解质微凝胶（无规和核壳）中可离子化基团的分布控制着与被捕获蛋白质的相互作用。聚两性电解质微凝胶能够根据 pH 值可逆地将其电荷从正电荷转变为负电荷。在这项工作中，我们合成了具有不同结构的聚两性电解质微凝胶，其具有受控数量和不同分布的酸性和碱性部分，作为胶体载体来研究模型蛋白细胞色素 c（cyt-c）的负载和释放。当微凝胶相对于蛋白质带相反电荷时，通过静电吸引在 pH 8 下首先将 cyt-c 负载到聚两性电解质微凝胶上。然后在不同 pH 值（3、6 和 8）下通过实验方法和分子动力学模拟研究蛋白质的释放。对于具有可离子化基团无规分布的微凝胶，由于静电排斥相互作用，观察到 cyt-c 的完全和加速（与聚电解质对应物相比）释放。对于具有确定可离子化基团的核壳结构微凝胶，可以通过形成带正电荷的壳将蛋白质困在中性核内，该壳起到静电势垒的作用。我们假设，这一发现允许设计具有编程释放动力学的功能性胶体载体，用于药物输送、催化和生物材料等应用。
