Remote Manipulation of Slidable Nano-Ligand Switch Regulates the Adhesion and Regenerative Polarization of Macrophages

Hyojun Choi; Gunhyu Bae; Chandra Khatua; Sunhong Min; Hee Joon Jung; Na Li; Indong Jun; Hui Wen Liu; Youngkyu Cho; Kyu Hwan Na; Minji Ko; Hongchul Shin; Yoon Hyuck Kim; Seok Chung; Jae-Jun Song; Vinayak P. Dravid; Heemin Kang

doi:10.1002/adfm.202001446

Remote Manipulation of Slidable Nano-Ligand Switch Regulates the Adhesion and Regenerative Polarization of Macrophages

Hyojun Choi, Gunhyu Bae, Chandra Khatua, Sunhong Min, Hee Joon Jung, Na Li, Indong Jun, Hui Wen Liu, Youngkyu Cho, Kyu Hwan Na, Minji Ko, Hongchul Shin, Yoon Hyuck Kim, Seok Chung, Jae-Jun Song, Vinayak P. Dravid, Heemin Kang

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24 Citations (Scopus)

Abstract

The development of materials capable of varying macroscale ligand distributions can emulate an extracellular matrix (ECM) remodeling and regulate the adhesion and polarization of macrophages. In this report, negatively charged slidable nano-ligands are assembled and then conjugated to a positively charged substrate via electrostatic interaction. The negatively charged slidable nano-ligands are prepared by coating magnetic nanoparticles with a polymer linker and negatively charged RGD ligand. The nano-ligand sliding is characterized under an external magnetic field, which spatiotemporally alters macroscale ligand density. To the best of knowledge, this is the first demonstration that magnetic maipulation of the macroscale ligand density inhibits inflammatory M1 phenotype but stimulates the adhesion and regenerative M2 phenotype of host macrophages. Furthermore, it is elucidated that the magnetic attraction of the slidable nano-ligand facilitates the assembly of adhesion structures in macrophages, thereby stimulating their regenerative M2 phenotype. The design of ECM-emulating materials that allow remote, spatiotemporal, and reversible controllability of macroscale ligand density provides an appealing strategy in the spatiotemporal regulation of immunomodulatory tissue-regenerative responses to implants in vivo.

Original language	English
Article number	2001446
Journal	Advanced Functional Materials
Volume	30
Issue number	35
DOIs	https://doi.org/10.1002/adfm.202001446
Publication status	Published - 2020 Aug 1

Bibliographical note

Funding Information:
H.C. and G.B. contributed equally to this work. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1F1A1058720). This work was also supported by a Korea University Grant. This work was also conducted at the Korea Basic Science Institute. 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 IRG2 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. All animals experiments were performed with approval from the Institutional Animal Care and Use Committee of Korea University.

Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

macrophage adhesion
macrophage polarization
macroscale ligand manipulation
reversible ligand sliding
slidable nano-ligand

ASJC Scopus subject areas

Chemistry(all)
Materials Science(all)
Condensed Matter Physics

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Choi, H., Bae, G., Khatua, C., Min, S., Jung, H. J., Li, N., Jun, I., Liu, H. W., Cho, Y., Na, K. H., Ko, M., Shin, H., Kim, Y. H., Chung, S., Song, J-J., Dravid, V. P., & Kang, H. (2020). Remote Manipulation of Slidable Nano-Ligand Switch Regulates the Adhesion and Regenerative Polarization of Macrophages. Advanced Functional Materials, 30(35), Article 2001446. https://doi.org/10.1002/adfm.202001446

Choi, H, Bae, G, Khatua, C, Min, S, Jung, HJ, Li, N, Jun, I, Liu, HW, Cho, Y, Na, KH, Ko, M, Shin, H, Kim, YH, Chung, S, Song, J-J, Dravid, VP & Kang, H 2020, 'Remote Manipulation of Slidable Nano-Ligand Switch Regulates the Adhesion and Regenerative Polarization of Macrophages', Advanced Functional Materials, vol. 30, no. 35, 2001446. https://doi.org/10.1002/adfm.202001446

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abstract = "The development of materials capable of varying macroscale ligand distributions can emulate an extracellular matrix (ECM) remodeling and regulate the adhesion and polarization of macrophages. In this report, negatively charged slidable nano-ligands are assembled and then conjugated to a positively charged substrate via electrostatic interaction. The negatively charged slidable nano-ligands are prepared by coating magnetic nanoparticles with a polymer linker and negatively charged RGD ligand. The nano-ligand sliding is characterized under an external magnetic field, which spatiotemporally alters macroscale ligand density. To the best of knowledge, this is the first demonstration that magnetic maipulation of the macroscale ligand density inhibits inflammatory M1 phenotype but stimulates the adhesion and regenerative M2 phenotype of host macrophages. Furthermore, it is elucidated that the magnetic attraction of the slidable nano-ligand facilitates the assembly of adhesion structures in macrophages, thereby stimulating their regenerative M2 phenotype. The design of ECM-emulating materials that allow remote, spatiotemporal, and reversible controllability of macroscale ligand density provides an appealing strategy in the spatiotemporal regulation of immunomodulatory tissue-regenerative responses to implants in vivo.",

keywords = "macrophage adhesion, macrophage polarization, macroscale ligand manipulation, reversible ligand sliding, slidable nano-ligand",

author = "Hyojun Choi and Gunhyu Bae and Chandra Khatua and Sunhong Min and Jung, {Hee Joon} and Na Li and Indong Jun and Liu, {Hui Wen} and Youngkyu Cho and Na, {Kyu Hwan} and Minji Ko and Hongchul Shin and Kim, {Yoon Hyuck} and Seok Chung and Jae-Jun Song and Dravid, {Vinayak P.} and Heemin Kang",

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T1 - Remote Manipulation of Slidable Nano-Ligand Switch Regulates the Adhesion and Regenerative Polarization of Macrophages

AU - Choi, Hyojun

AU - Bae, Gunhyu

AU - Khatua, Chandra

AU - Min, Sunhong

AU - Jung, Hee Joon

AU - Li, Na

AU - Jun, Indong

AU - Liu, Hui Wen

AU - Cho, Youngkyu

AU - Na, Kyu Hwan

AU - Ko, Minji

AU - Shin, Hongchul

AU - Kim, Yoon Hyuck

AU - Chung, Seok

AU - Song, Jae-Jun

AU - Dravid, Vinayak P.

AU - Kang, Heemin

N1 - Funding Information: H.C. and G.B. contributed equally to this work. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1F1A1058720). This work was also supported by a Korea University Grant. This work was also conducted at the Korea Basic Science Institute. 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 IRG2 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. All animals experiments were performed with approval from the Institutional Animal Care and Use Committee of Korea University. Publisher Copyright: © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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N2 - The development of materials capable of varying macroscale ligand distributions can emulate an extracellular matrix (ECM) remodeling and regulate the adhesion and polarization of macrophages. In this report, negatively charged slidable nano-ligands are assembled and then conjugated to a positively charged substrate via electrostatic interaction. The negatively charged slidable nano-ligands are prepared by coating magnetic nanoparticles with a polymer linker and negatively charged RGD ligand. The nano-ligand sliding is characterized under an external magnetic field, which spatiotemporally alters macroscale ligand density. To the best of knowledge, this is the first demonstration that magnetic maipulation of the macroscale ligand density inhibits inflammatory M1 phenotype but stimulates the adhesion and regenerative M2 phenotype of host macrophages. Furthermore, it is elucidated that the magnetic attraction of the slidable nano-ligand facilitates the assembly of adhesion structures in macrophages, thereby stimulating their regenerative M2 phenotype. The design of ECM-emulating materials that allow remote, spatiotemporal, and reversible controllability of macroscale ligand density provides an appealing strategy in the spatiotemporal regulation of immunomodulatory tissue-regenerative responses to implants in vivo.

AB - The development of materials capable of varying macroscale ligand distributions can emulate an extracellular matrix (ECM) remodeling and regulate the adhesion and polarization of macrophages. In this report, negatively charged slidable nano-ligands are assembled and then conjugated to a positively charged substrate via electrostatic interaction. The negatively charged slidable nano-ligands are prepared by coating magnetic nanoparticles with a polymer linker and negatively charged RGD ligand. The nano-ligand sliding is characterized under an external magnetic field, which spatiotemporally alters macroscale ligand density. To the best of knowledge, this is the first demonstration that magnetic maipulation of the macroscale ligand density inhibits inflammatory M1 phenotype but stimulates the adhesion and regenerative M2 phenotype of host macrophages. Furthermore, it is elucidated that the magnetic attraction of the slidable nano-ligand facilitates the assembly of adhesion structures in macrophages, thereby stimulating their regenerative M2 phenotype. The design of ECM-emulating materials that allow remote, spatiotemporal, and reversible controllability of macroscale ligand density provides an appealing strategy in the spatiotemporal regulation of immunomodulatory tissue-regenerative responses to implants in vivo.

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Remote Manipulation of Slidable Nano-Ligand Switch Regulates the Adhesion and Regenerative Polarization of Macrophages

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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