title: A magnetic nanoparticles relaxation sensor for protein-protein interaction detection at ultra-low magnetic field.
abstract: Functionalized magnetic nanoparticles (MNPs) can serve as magnetic relaxation sensors (MRSs) to detect different biological targets, because the clustering of magnetic particle may cause the spin-spin relaxation time (T2) decrease of the surrounding water protons. However, the application of MNPs in clinical NMR systems faces the challenge of poor stability at magnetic field strengths in the order of tesla. The recently developed ultra-low field (ULF) NMR technique working at microtesla (μT) range then becomes a candidate. Herein, we incorporated superconducting quantum interference device (SQUID) as the detector in the ultra-low field system to enhance the sensitivity. We functionalized the Fe3O4 nanoparticles with the gama-aminobutyrate type A receptor-associated proteins (GABARAP), which specifically interact with calreticulin (CRT). As a result of the interaction between GABARAP and CRT, the clustering of the functionalized MNPs generates local magnetic fields, which accelerate the dephasing of the water protons in the vicinity. We analyzed the relation between T2 values and the CRT concentrations at 211μT and the low detection limit for CRT is 10 pg/ml, which is superior to the immunoblot system. The high sensitivity of the ULF NMR system for protein-protein interaction detection demonstrates the potential to use this inexpensive, portable system for quick biochemical and clinical assays.
authors.affiliation: State Key Laboratory Cultivation Base for Nonmetal Composites and Functional Materials, School of Materials Science and Engineering, Southwest University of Science and Technology, 621010 Mianyang, Sichuan, China; Peter Gruenberg Institute (PGI-8), Research Center Juelich, 52425 Juelich, Germany. Electronic address: w.wang@swust.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Complex Systems (ICS-6), Research Center Juelich, 52425 Juelich, Germany; Shanghai Institute for Advanced Immunological Studies, ShanghaiTech University, Shanghai 200031, China.
authors.forename: Peixiang
authors.initials: P
authors.lastname: Ma
authors.affiliation: State key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, 200050 Shanghai, China. Electronic address: donghui@mail.simc.ac.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Peter Gruenberg Institute (PGI-8), Research Center Juelich, 52425 Juelich, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Krause
authors.affiliation: Peter Gruenberg Institute (PGI-8), Research Center Juelich, 52425 Juelich, Germany.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Complex Systems (ICS-6), Research Center Juelich, 52425 Juelich, Germany; Institute of Physical Biology, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.affiliation: Peter Gruenberg Institute (PGI-8), Research Center Juelich, 52425 Juelich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Offenhaeusser
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, 610064 Chengdu, China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
mesh_terms: D015374:Biosensing Techniques; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D011485:Protein Binding; D060066:Protein Interaction Maps; D011506:Proteins / Q000302:isolation & purification* / Q000378:metabolism
chemical_list: D058185:Magnetite Nanoparticles; D011506:Proteins
keywords: Magnetic nanoparticles (MNPs); Protein detection; Relaxation time; SQUID-based ultra-low field; Silane coating method