TY - JOUR
T1 - An In Situ Reversible Heterodimeric Nanoswitch Controlled by Metal-Ion–Ligand Coordination Regulates the Mechanosensing and Differentiation of Stem Cells
AU - Kang, Heemin
AU - Zhang, Kunyu
AU - Jung, Hee Joon
AU - Yang, Boguang
AU - Chen, Xiaoyu
AU - Pan, Qi
AU - Li, Rui
AU - Xu, Xiayi
AU - Li, Gang
AU - Dravid, Vinayak P.
AU - Bian, Liming
N1 - Funding Information:
H.K and K.Z. contributed equally to this work. Project 31570979 is supported by the National Natural Science Foundation of China. This work is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (project nos. 14202215, 14220716); the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (04152836); the Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong; the CRF project (project no. C6021-14E) in MCPF of HKUST. The work was partially supported by Hong Kong Research Grants Council Theme-based Research Scheme (Ref. T13-402/17-N). This work made use of the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. The animal experiments were carried out after the approval of the Institutional Animal Care and Use Committee of the Chinese University of Hong Kong.
Funding Information:
H.K and K.Z. contributed equally to this work. Project 31570979 is supported by the National Natural Science Foundation of China. This work is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (project nos. 14202215, 14220716); the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (04152836); the Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong; the CRF project (project no. C6021-14E) in MCPF of HKUST. The work was partially supported by Hong Kong Research Grants Council Theme-based Research Scheme (Ref. T13-402/17-N). This work made use of the EPIC facility of Northwestern University's NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. The animal experiments were carried out after the approval of the Institutional Animal Care and Use Committee of the Chinese University of Hong Kong.
Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/11/2
Y1 - 2018/11/2
N2 - 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.
AB - 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.
KW - in situ nanoswitches
KW - in vivo cell adhesion
KW - in vivo cell release
KW - metal-ion–ligand coordination
KW - reversible heterodimers
UR - http://www.scopus.com/inward/record.url?scp=85053443020&partnerID=8YFLogxK
U2 - 10.1002/adma.201803591
DO - 10.1002/adma.201803591
M3 - Article
C2 - 30277606
AN - SCOPUS:85053443020
SN - 0935-9648
VL - 30
JO - Advanced Materials
JF - Advanced Materials
IS - 44
M1 - 1803591
ER -