An In Situ Reversible Heterodimeric Nanoswitch Controlled by Metal-Ion-Ligand Coordination Regulates the Mechanosensing and Differentiation of Stem Cells

被引:48
作者
Kang, Heemin [1 ]
Zhang, Kunyu [1 ]
Jung, Hee Joon [2 ,3 ,4 ]
Yang, Boguang [1 ]
Chen, Xiaoyu [1 ]
Pan, Qi [5 ]
Li, Rui [1 ]
Xu, Xiayi [1 ]
Li, Gang [5 ,6 ]
Dravid, Vinayak P. [2 ,3 ,4 ]
Bian, Liming [1 ,6 ]
机构
[1] Chinese Univ Hong Kong, Dept Biomed Engn, Hong Kong 999077, Hong Kong, Peoples R China
[2] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA
[3] Int Inst Nanotechnol, Evanston, IL 60208 USA
[4] Northwestern Univ, NUANCE Ctr, Evanston, IL 60208 USA
[5] Chinese Univ Hong Kong, Prince Wales Hosp, Fac Med, Dept Orthopaed & Traumatol, Hong Kong 999077, Hong Kong, Peoples R China
[6] Chinese Univ Hong Kong, Shenzhen Res Inst, Shenzhen 518172, Peoples R China
基金
中国国家自然科学基金;
关键词
in situ nanoswitches; in vivo cell adhesion; in vivo cell release; metal-ion-ligand coordination; reversible heterodimers; ADHESION; MECHANOTRANSDUCTION; MECHANISM; SURFACES; CAPTURE; RELEASE; MATRIX;
D O I
10.1002/adma.201803591
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
In situ and cytocompatible nanoswitching by external stimuli is highly appealing for reversibly regulating cellular adhesion and functions in vivo. Here, a heterodimeric nanoswitch is designed to facilitate in situ switchable and combinatorial presentation of integrin-binding cell-adhesive moieties, such as Mg2+ and Arg-Gly-Asp (RGD) ligand in nanostructures. In situ reversible nanoswitching is controlled by convertible coordination between bioactive Mg2+ and bisphosphonate (BP) ligand. A BP-coated gold-nanoparticle monomer (BP-AuNP) on a substrate is prepared to allow in situ assembly of cell-adhesive Mg2+-active Mg-BP nanoparticles (NPs) on a BP-AuNP surface via Mg2+-BP coordination, yielding heterodimeric nanostructures (switching "ON"). Ethylenediaminetetraacetic acid (EDTA)-based Mg2+ chelation allows in situ disassembly of Mg2+-BP NP, reverting to Mg2+-free monomer (switching "OFF"). This in situ reversible nanoswitching on and off of cell-adhesive Mg2+ presentation allows reversible cell adhesion and release in vivo, respectively, and spatiotemporally controls cyclic cell adhesion. In situ heterodimeric assembly of dual RGD ligand- and Mg2+-active RGD-BP-Mg2+ NP (switching "Dual ON") further tunes and promotes focal adhesion, spreading, and differentiation of stem cells. The modular nature of this in situ nanoswitch can accommodate various bioactive nanostructures via metal-ion-ligand coordination to regulate diverse cellular functions in vivo in reversible and compatible manner.
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页数:8
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