Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

Hyunsik Hong; Sunhong Min; Sagang Koo; Yunjung Lee; Jinho Yoon; Woo Young Jang; Nayeon Kang; Ramar Thangam; Hyojun Choi; Hee Joon Jung; Seong Beom Han; Qiang Wei; Seung Ho Yu; Dong Hwee Kim; Ramasamy Paulmurugan; Woong-Kyo Jeong; Ki Bum Lee; Taeghwan Hyeon; Dokyoon Kim; Heemin Kang

doi:10.1002/adma.202105460

Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

Hyunsik Hong, Sunhong Min, Sagang Koo, Yunjung Lee, Jinho Yoon, Woo Young Jang, Nayeon Kang, Ramar Thangam, Hyojun Choi, Hee Joon Jung, Seong Beom Han, Qiang Wei, Seung Ho Yu, Dong Hwee Kim, Ramasamy Paulmurugan, Woong-Kyo Jeong, Ki Bum Lee, Taeghwan Hyeon, Dokyoon Kim, Heemin Kang

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

22 Citations (Scopus)

Abstract

In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly-based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell-adhesive motif)-presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair.

Original language	English
Article number	2105460
Journal	Advanced Materials
Volume	34
Issue number	2
DOIs	https://doi.org/10.1002/adma.202105460
Publication status	Published - 2022 Jan 13

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1C1C1011038 and 2019R1F1A1060107). This work was also supported by a Korea University Grant. HAADF-STEM imaging was conducted with the support of the Seoul Center in Korea Basic Science Institute (KBSI). 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.

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1C1C1011038 and 2019R1F1A1060107). This work was also supported by a Korea University Grant. HAADF‐STEM imaging was conducted with the support of the Seoul Center in Korea Basic Science Institute (KBSI). 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.

Publisher Copyright:
© 2021 Wiley-VCH GmbH

ASJC Scopus subject areas

Materials Science(all)
Mechanics of Materials
Mechanical Engineering

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10.1002/adma.202105460

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Hong, H., Min, S., Koo, S., Lee, Y., Yoon, J., Jang, W. Y., Kang, N., Thangam, R., Choi, H., Jung, H. J., Han, S. B., Wei, Q., Yu, S. H., Kim, D. H., Paulmurugan, R., Jeong, W-K., Lee, K. B., Hyeon, T., Kim, D., & Kang, H. (2022). Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation. Advanced Materials, 34(2), Article 2105460. https://doi.org/10.1002/adma.202105460

@article{a3c2e74bbc674c5389cd3f6304f932a1,

title = "Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation",

abstract = "In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly-based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell-adhesive motif)-presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair.",

author = "Hyunsik Hong and Sunhong Min and Sagang Koo and Yunjung Lee and Jinho Yoon and Jang, {Woo Young} and Nayeon Kang and Ramar Thangam and Hyojun Choi and Jung, {Hee Joon} and Han, {Seong Beom} and Qiang Wei and Yu, {Seung Ho} and Kim, {Dong Hwee} and Ramasamy Paulmurugan and Woong-Kyo Jeong and Lee, {Ki Bum} and Taeghwan Hyeon and Dokyoon Kim and Heemin Kang",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1C1C1011038 and 2019R1F1A1060107). This work was also supported by a Korea University Grant. HAADF-STEM imaging was conducted with the support of the Seoul Center in Korea Basic Science Institute (KBSI). 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. Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1C1C1011038 and 2019R1F1A1060107). This work was also supported by a Korea University Grant. HAADF‐STEM imaging was conducted with the support of the Seoul Center in Korea Basic Science Institute (KBSI). 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. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",

year = "2022",

month = jan,

day = "13",

doi = "10.1002/adma.202105460",

language = "English",

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T1 - Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

AU - Hong, Hyunsik

AU - Min, Sunhong

AU - Koo, Sagang

AU - Lee, Yunjung

AU - Yoon, Jinho

AU - Jang, Woo Young

AU - Kang, Nayeon

AU - Thangam, Ramar

AU - Choi, Hyojun

AU - Jung, Hee Joon

AU - Han, Seong Beom

AU - Wei, Qiang

AU - Yu, Seung Ho

AU - Kim, Dong Hwee

AU - Paulmurugan, Ramasamy

AU - Jeong, Woong-Kyo

AU - Lee, Ki Bum

AU - Hyeon, Taeghwan

AU - Kim, Dokyoon

AU - Kang, Heemin

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1C1C1011038 and 2019R1F1A1060107). This work was also supported by a Korea University Grant. HAADF-STEM imaging was conducted with the support of the Seoul Center in Korea Basic Science Institute (KBSI). 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. Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1C1C1011038 and 2019R1F1A1060107). This work was also supported by a Korea University Grant. HAADF‐STEM imaging was conducted with the support of the Seoul Center in Korea Basic Science Institute (KBSI). 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. Publisher Copyright: © 2021 Wiley-VCH GmbH

PY - 2022/1/13

Y1 - 2022/1/13

N2 - In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly-based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell-adhesive motif)-presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair.

AB - In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly-based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell-adhesive motif)-presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair.

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DO - 10.1002/adma.202105460

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ER -

Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

Abstract

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