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Adv Mater. 2018 Nov;30(44):e1803591. doi: 10.1002/adma.201803591. Epub 2018 Sep 16.

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

Kang H1, Zhang K1, Jung HJ2,3,4, Yang B1, Chen X1, Pan Q5, Li R1, Xu X1, Li G5,6, Dravid VP2,3,4, Bian L1,6.

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Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, 999077, China.
Department of Materials Science and Engineering, Northwestern University, Evanston, IL, 60208, USA.
International Institute for Nanotechnology, Evanston, IL, 60208, USA.
NUANCE Center, Northwestern University, Evanston, IL, 60208, USA.
Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, 999077, China.
Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, 518172, China.


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.


in situ nanoswitches; in vivo cell adhesion; in vivo cell release; metal-ion-ligand coordination; reversible heterodimers

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