受限纳尺度下蛋白质输运的主动操纵技术  

Proactive Manipulation Techniques for Protein Transport at Confined Nanoscale

作　　者：马超凡 徐伟 刘巍[1,2] 徐昌晖[1,2] 沙菁㛃[1,2] Ma Chaofan;Xu Wei;Liu Wei;Xu Changhui;Sha Jingjie(School of Mechanical Engineering,Southeast University,Nanjing 211189;Jiangsu Key Laboratory for Design and Manufacture of Micro-nano Biomedical Instruments,Southeast University,Nanjing 211189)

机构地区：[1]东南大学机械工程学院,南京211189 [2]东南大学、江苏省微纳生物医学仪器设计与制造重点实验室,南京211189

出　　处：《化学学报》2023年第7期857-868,共12页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.52075099,52035003)资助。

摘　　要：蛋白质是人体细胞、组织的重要组成部分,与众多代谢活动密切相关,它们的一些微小改变就可能引发人体的重大疾病.因此,蛋白质检测是生物化学领域的重要课题.纳米孔技术能够在单分子水平甚至单氨基酸水平上实时检测蛋白质,有望成为最低成本和最高效的蛋白质检测方法之一.然而,使用纳米孔检测蛋白质时,由于实验条件和检测策略的原因,使得蛋白质在纳米孔中驻留时间过短,无法从蛋白质捕获的电信号中清晰地反映更多的生物细节信息.解决这一问题的关键在于控制蛋白质通过纳米孔时的输运速度,满足传感器件带宽的要求.本综述从外部力场竞争、内部力场相互作用、亲疏水相互作用、空间位阻效应等角度综述了蛋白质在纳米孔中输运的主动操纵技术,目的是提高纳米孔对蛋白质的捕获频率,延长蛋白质在纳米孔内的驻留时间,以实现高分辨率的蛋白质检测,充分揭示蛋白质分子的构象变化机制、反应动力学,甚至实现蛋白质测序等.最后对纳米孔传感技术在蛋白质检测方面存在的巨大挑战和发展趋势进行了详细展望和总结阐述.Proteins are important components of human cells and tissues and are closely related to numerous metabolic activities,and some small changes in them may trigger major diseases in the human body.Therefore,protein detection is an important topic in the field of biochemistry.Nanopore technology is capable of real-time protein detection at the single molecule level or even at the single amino acid level,and is expected to be one of the lowest costs and most efficient protein detection methods.However,when using nanopores to detect proteins,the experimental conditions and detection strategy make the protein residence time in the nanopore too short to clearly reflect more detailed biological information from the electrical signal captured by the protein.The critical solution to this problem lies in controlling the transport rate of proteins through the nanopore to meet the bandwidth of the sensor device.In this paper,the active manipulation techniques of protein transport in nanopores are reviewed from the perspectives of external force field competition,internal force field interaction,hydrophilic interaction,and spatial resistance effect,with the aim of improving the capture frequency of proteins by nanopores and prolonging the residence time of proteins in nanopores to achieve high-resolution protein detection,fully reveal the conformational change mechanism of protein molecules,reaction kinetics,and even realize protein sequencing,etc.Finally,the great challenges and development trends of nanopore sensing technology for protein detection are described in detail.

关 键 词：蛋白质检测 纳米孔 操纵方法 捕获时间 纳尺度输运 

分 类 号：Q51[生物学—生物化学]