在自然界中，离子通道在控制细胞与其周围环境之间的离子传输中起关键作用。钙离子（Ca2+）诱导的Ca2+释放（CICR）是Ca2+通道的关键控制机制，发生在与兰尼碱受体协同作用的Ca2+浓度梯度调控中，其被称为“钙火花”。受这种自我调节的生物过程的启发，通过融合聚{N-异丙基丙烯酰胺-co-丙烯酰胺-[4-(三氟甲基)苯基]-2-硫脲0.2-co-丙烯酰胺，开发了一种智能Ca2+浓度调节的纳米通道系统。PNI-co-CF3-PT0.2-co-DDDEEKC0.2的三组分共聚物被接枝在多孔阳极氧化铝（PAA）膜的纳米通道上。在这种智能聚合物设计中，DDDEEKC七肽单元通过配位键与Ca2+具有超强的结合亲和力，而CF3-PT作为氢键调节单元起作用，促进PNI主链响应Ca2+特异性吸附引起的显著构象转变。由于这些特征，修饰的纳米通道的动态跨膜行为可以通过Ca2+浓度精确控制。此外，敏感的Ca2+响应性低至10 pM，对Ca2+的高特异性能够区分Ca2+与其他潜在的干扰金属离子（如K+，Cu2+，Mg2+，Zn2+，Fe3+和Al3+），纳米通道的显着形态变化，以及令人满意的可逆性，表明Ca2+响应性聚合物在生物芯片和人造纳米通道的构筑中具有巨大的潜力。

Smart Polymer–Based Calcium Ion Self-Regulated Nanochannel by Mimicking Biological Ca2+–induced Ca2+ Release Process. 

Yunlong Li, Yuting Xiong, Dongdong Wang, Xiuling Li, Zhixiang Chen, Cunli Wang, Haijuan Qin, Jinxuan Liu, Baisong Chang, and Guangyan Qing*

NPG Asia Materials 2019, 11, 46.

DOI: 10.1038/s41427-019-0148-4

In nature, ion channels play key roles in controlling ion transport between cells and their surroundings. Calcium ion (Ca²⁺)–induced Ca²⁺ release (CICR), being a critical control mechanism for Ca²⁺ channels, occurs as a Ca²⁺ concentration gradient working in synergy with ryanodine receptors, which is famous as “calcium sparks”. Inspired by this self-regulated biological process, a smart Ca²⁺ concentration–modulated nanochannel system was developed by integrating a poly{N-isopropylacrylamide-co-acrylamide-[4-(trifluoromethyl) phenyl]-2-thiourea_0.2-co-acrylamide-DDDEEKC_0.2} (denoted as PNI-co-CF₃-PT_0.2-co-DDDEEKC_0.2) three-component copolymer onto nanochannels of porous anodic alumina (PAA) membrane. In this smart polymer design, DDDEEKC hepta-peptide unit has an extraordinary binding affinity with Ca²⁺ through coordination bonds, while CF₃-PT functions as a hydrogen bond mediation unit, facilitating a remarkable conformational transition of the PNI main chain in response to the Ca²⁺ specific adsorption. Due to these futures, dynamic gating behaviors of the modified nanochannels could be precisely manipulated by Ca²⁺ concentration. In addition, sensitive Ca²⁺ responsiveness as low as 10 pM, high specificity toward Ca²⁺ capable of discriminating Ca²⁺ from other potential interference metal ions (e.g., K⁺, Cu²⁺, Mg²⁺, Zn²⁺, Fe³⁺, and Al³⁺), remarkable morphological change in the nanochannel as well as satisfactory reversibility, indicates the great potential of Ca²⁺–responsive polymers in the fabrication of bio-devices and artificial nanochannels.