Receptor-Level Proximity and Fastening of Ligands Modulates Stem Cell Differentiation

Gunhyu Bae, Myeong Soo Kim, Ramar Thangam, Thomas Myeongseok Koo, Woo Young Jang, Jinho Yoon, Seong Beom Han, Letao Yang, Seong Yeol Kim, Nayeon Kang, Sunhong Min, Hyunsik Hong, Hong En Fu, Min Jun Ko, Dong Hwee Kim, Woong Kyo Jeong, Dong Hyun Kim, Tae Hyung Kim, Jeong Woo Choi, Ki Bum LeeRamasamy Paulmurugan, Yangzhi Zhu, Han Jun Kim, Junmin Lee, Jong Seung Kim, Ali Khademhosseini, Young Keun Kim, Heemin Kang

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Cellular adhesion is regulated by the binding of 10 nm sized integrin to Arg-Gly-Asp (RGD) ligands present in extracellular matrix proteins. In this study, seed-mediated growth of gold nanoparticles (AuNPs) on the surface of iron oxide (Fe₃O₄) nanotemplates is employed to tune the diameter and interdistance of RGD-bearing AuNPs at the receptor-level. The Fe₃O₄ nanotemplates decorated with RGD-bearing AuNPs arranged in various RGD diameters and interdistances at the receptor-levels are flexibly fastened to a substrate. Similar to fully connected RGDs, subreceptor-level-gapped (quasiconnected) RGDs activate integrin binding with the adjacent RGDs, which stimulates focal adhesion, mechanosensing, and differentiation of stem cells. This stimulation of stem cells is hindered when the RGD interdistance increases above the receptor-level gap. However, this stimulation is partially effective when the RGD diameter also increases far above the receptor-level gap. Strikingly, magnetically attracted fastening of the RGDs toward the substrate via polymer linker tightening fully stimulates adhesion and differentiation of stem cells in a reversible manner, both in vitro and in vivo. Various RGD diameter and interdistance on Fe₃O₄ nanotemplates can further elucidate the dynamic receptor-level RGD proximity-regulated stem cell differentiation that govern tissue repair.

Original language	English
Article number	2200828
Journal	Advanced Functional Materials
Volume	32
Issue number	30
DOIs	https://doi.org/10.1002/adfm.202200828
Publication status	Published - 2022 Jul 25

Bibliographical note

Publisher Copyright:
© 2022 Wiley-VCH GmbH.

Keywords

integrin clustering
ligand fastening
ligand proximity
stem cell adhesion
stem cell differentiation

ASJC Scopus subject areas

Electronic, Optical and Magnetic Materials
General Chemistry
Biomaterials
General Materials Science
Condensed Matter Physics
Electrochemistry

Access to Document

10.1002/adfm.202200828

Cite this

Bae, G., Kim, M. S., Thangam, R., Koo, T. M., Jang, W. Y., Yoon, J., Han, S. B., Yang, L., Kim, S. Y., Kang, N., Min, S., Hong, H., Fu, H. E., Ko, M. J., Kim, D. H., Jeong, W. K., Kim, D. H., Kim, T. H., Choi, J. W., ... Kang, H. (2022). Receptor-Level Proximity and Fastening of Ligands Modulates Stem Cell Differentiation. Advanced Functional Materials, 32(30), Article 2200828. https://doi.org/10.1002/adfm.202200828

Bae, G, Kim, MS, Thangam, R, Koo, TM, Jang, WY, Yoon, J, Han, SB, Yang, L, Kim, SY, Kang, N, Min, S, Hong, H, Fu, HE, Ko, MJ, Kim, DH, Jeong, WK, Kim, DH, Kim, TH, Choi, JW, Lee, KB, Paulmurugan, R, Zhu, Y, Kim, HJ, Lee, J, Kim, JS, Khademhosseini, A, Kim, YK & Kang, H 2022, 'Receptor-Level Proximity and Fastening of Ligands Modulates Stem Cell Differentiation', Advanced Functional Materials, vol. 32, no. 30, 2200828. https://doi.org/10.1002/adfm.202200828

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title = "Receptor-Level Proximity and Fastening of Ligands Modulates Stem Cell Differentiation",

abstract = "Cellular adhesion is regulated by the binding of 10 nm sized integrin to Arg-Gly-Asp (RGD) ligands present in extracellular matrix proteins. In this study, seed-mediated growth of gold nanoparticles (AuNPs) on the surface of iron oxide (Fe3O4) nanotemplates is employed to tune the diameter and interdistance of RGD-bearing AuNPs at the receptor-level. The Fe3O4 nanotemplates decorated with RGD-bearing AuNPs arranged in various RGD diameters and interdistances at the receptor-levels are flexibly fastened to a substrate. Similar to fully connected RGDs, subreceptor-level-gapped (quasiconnected) RGDs activate integrin binding with the adjacent RGDs, which stimulates focal adhesion, mechanosensing, and differentiation of stem cells. This stimulation of stem cells is hindered when the RGD interdistance increases above the receptor-level gap. However, this stimulation is partially effective when the RGD diameter also increases far above the receptor-level gap. Strikingly, magnetically attracted fastening of the RGDs toward the substrate via polymer linker tightening fully stimulates adhesion and differentiation of stem cells in a reversible manner, both in vitro and in vivo. Various RGD diameter and interdistance on Fe3O4 nanotemplates can further elucidate the dynamic receptor-level RGD proximity-regulated stem cell differentiation that govern tissue repair.",

keywords = "integrin clustering, ligand fastening, ligand proximity, stem cell adhesion, stem cell differentiation",

author = "Gunhyu Bae and Kim, {Myeong Soo} and Ramar Thangam and Koo, {Thomas Myeongseok} and Jang, {Woo Young} and Jinho Yoon and Han, {Seong Beom} and Letao Yang and Kim, {Seong Yeol} and Nayeon Kang and Sunhong Min and Hyunsik Hong and Fu, {Hong En} and Ko, {Min Jun} and Kim, {Dong Hwee} and Jeong, {Woong Kyo} and Kim, {Dong Hyun} and Kim, {Tae Hyung} and Choi, {Jeong Woo} and Lee, {Ki Bum} and Ramasamy Paulmurugan and Yangzhi Zhu and Kim, {Han Jun} and Junmin Lee and Kim, {Jong Seung} and Ali Khademhosseini and Kim, {Young Keun} and Heemin Kang",

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AU - Bae, Gunhyu

AU - Kim, Myeong Soo

AU - Thangam, Ramar

AU - Koo, Thomas Myeongseok

AU - Jang, Woo Young

AU - Yoon, Jinho

AU - Han, Seong Beom

AU - Yang, Letao

AU - Kim, Seong Yeol

AU - Kang, Nayeon

AU - Min, Sunhong

AU - Hong, Hyunsik

AU - Fu, Hong En

AU - Ko, Min Jun

AU - Kim, Dong Hwee

AU - Jeong, Woong Kyo

AU - Kim, Dong Hyun

AU - Kim, Tae Hyung

AU - Choi, Jeong Woo

AU - Lee, Ki Bum

AU - Paulmurugan, Ramasamy

AU - Zhu, Yangzhi

AU - Kim, Han Jun

AU - Lee, Junmin

AU - Kim, Jong Seung

AU - Khademhosseini, Ali

AU - Kim, Young Keun

AU - Kang, Heemin

PY - 2022/7/25

Y1 - 2022/7/25

N2 - Cellular adhesion is regulated by the binding of 10 nm sized integrin to Arg-Gly-Asp (RGD) ligands present in extracellular matrix proteins. In this study, seed-mediated growth of gold nanoparticles (AuNPs) on the surface of iron oxide (Fe3O4) nanotemplates is employed to tune the diameter and interdistance of RGD-bearing AuNPs at the receptor-level. The Fe3O4 nanotemplates decorated with RGD-bearing AuNPs arranged in various RGD diameters and interdistances at the receptor-levels are flexibly fastened to a substrate. Similar to fully connected RGDs, subreceptor-level-gapped (quasiconnected) RGDs activate integrin binding with the adjacent RGDs, which stimulates focal adhesion, mechanosensing, and differentiation of stem cells. This stimulation of stem cells is hindered when the RGD interdistance increases above the receptor-level gap. However, this stimulation is partially effective when the RGD diameter also increases far above the receptor-level gap. Strikingly, magnetically attracted fastening of the RGDs toward the substrate via polymer linker tightening fully stimulates adhesion and differentiation of stem cells in a reversible manner, both in vitro and in vivo. Various RGD diameter and interdistance on Fe3O4 nanotemplates can further elucidate the dynamic receptor-level RGD proximity-regulated stem cell differentiation that govern tissue repair.

AB - Cellular adhesion is regulated by the binding of 10 nm sized integrin to Arg-Gly-Asp (RGD) ligands present in extracellular matrix proteins. In this study, seed-mediated growth of gold nanoparticles (AuNPs) on the surface of iron oxide (Fe3O4) nanotemplates is employed to tune the diameter and interdistance of RGD-bearing AuNPs at the receptor-level. The Fe3O4 nanotemplates decorated with RGD-bearing AuNPs arranged in various RGD diameters and interdistances at the receptor-levels are flexibly fastened to a substrate. Similar to fully connected RGDs, subreceptor-level-gapped (quasiconnected) RGDs activate integrin binding with the adjacent RGDs, which stimulates focal adhesion, mechanosensing, and differentiation of stem cells. This stimulation of stem cells is hindered when the RGD interdistance increases above the receptor-level gap. However, this stimulation is partially effective when the RGD diameter also increases far above the receptor-level gap. Strikingly, magnetically attracted fastening of the RGDs toward the substrate via polymer linker tightening fully stimulates adhesion and differentiation of stem cells in a reversible manner, both in vitro and in vivo. Various RGD diameter and interdistance on Fe3O4 nanotemplates can further elucidate the dynamic receptor-level RGD proximity-regulated stem cell differentiation that govern tissue repair.

KW - integrin clustering

KW - ligand fastening

KW - ligand proximity

KW - stem cell adhesion

KW - stem cell differentiation

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