Independent Tuning of Nano-Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells

Sunhong Min; Yoo Sang Jeon; Hee Joon Jung; Chandra Khatua; Na Li; Gunhyu Bae; Hyojun Choi; Hyunsik Hong; Jeong Eun Shin; Min Jun Ko; Han Seok Ko; Indong Jun; Hong En Fu; Seung Hyun Kim; Ramar Thangam; Jae Jun Song; Vinayak P. Dravid; Young Keun Kim; Heemin Kang

doi:10.1002/adma.202004300

Independent Tuning of Nano-Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells

Sunhong Min, Yoo Sang Jeon, Hee Joon Jung, Chandra Khatua, Na Li, Gunhyu Bae, Hyojun Choi, Hyunsik Hong, Jeong Eun Shin, Min Jun Ko, Han Seok Ko, Indong Jun, Hong En Fu, Seung Hyun Kim, Ramar Thangam, Jae Jun Song, Vinayak P. Dravid, Young Keun Kim^*, Heemin Kang^*

^*Corresponding author for this work

Materials Science and Engineering

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

37 Scopus citations

Abstract

The native extracellular matrix (ECM) can exhibit heterogeneous nano-sequences periodically displaying ligands to regulate complex cell–material interactions in vivo. Herein, an ECM-emulating heterogeneous barcoding system, including ligand-bearing Au and ligand-free Fe nano-segments, is developed to independently present tunable frequency and sequences in nano-segments of cell-adhesive RGD ligand. Specifically, similar exposed surface areas of total Fe and Au nano-segments are designed. Fe segments are used for substrate coupling of nanobarcodes and as ligand-free nano-segments and Au segments for ligand coating while maintaining both nanoscale (local) and macroscale (total) ligand density constant in all groups. Low nano-ligand frequency in the same sequences and terminally sequenced nano-ligands at the same frequency independently facilitate focal adhesion and mechanosensing of stem cells, which are collectively effective both in vitro and in vivo, thereby inducing stem cell differentiation. The Fe/RGD-Au nanobarcode implants exhibit high stability and no local and systemic toxicity in various tissues and organs in vivo. This work sheds novel insight into designing biomaterials with heterogeneous nano-ligand sequences at terminal sides and/or low frequency to facilitate cellular adhesion. Tuning the electrodeposition conditions can allow synthesis of unlimited combinations of ligand nano-sequences and frequencies, magnetic elements, and bioactive ligands to remotely regulate numerous host cells in vivo.

Original language	English (US)
Article number	2004300
Journal	Advanced Materials
Volume	32
Issue number	40
DOIs	https://doi.org/10.1002/adma.202004300
State	Published - Oct 1 2020

Funding

S.M., Y.J., and H.J. 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. 2020R1C1C1011038 and 2019R1A2C3006587). This work was also supported by a Korea University Grant. HADDF‐STEM imaging was conducted with the support of 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. Animal experiments were approved by the Institutional Animal Care and Use Committee of Korea University. Human mesenchymal stem cells (passage 5) were obtained from Lonza.

Keywords

cell adhesion
nano-ligand frequencies
nano-ligand sequences
stem cell differentiation
unlimited nanobarcode tunability

ASJC Scopus subject areas

General Materials Science
Mechanics of Materials
Mechanical Engineering

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Cite this

Min, S., Jeon, Y. S., Jung, H. J., Khatua, C., Li, N., Bae, G., Choi, H., Hong, H., Shin, J. E., Ko, M. J., Ko, H. S., Jun, I., Fu, H. E., Kim, S. H., Thangam, R., Song, J. J., Dravid, V. P., Kim, Y. K., & Kang, H. (2020). Independent Tuning of Nano-Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells. Advanced Materials, 32(40), Article 2004300. https://doi.org/10.1002/adma.202004300

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title = "Independent Tuning of Nano-Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells",

abstract = "The native extracellular matrix (ECM) can exhibit heterogeneous nano-sequences periodically displaying ligands to regulate complex cell–material interactions in vivo. Herein, an ECM-emulating heterogeneous barcoding system, including ligand-bearing Au and ligand-free Fe nano-segments, is developed to independently present tunable frequency and sequences in nano-segments of cell-adhesive RGD ligand. Specifically, similar exposed surface areas of total Fe and Au nano-segments are designed. Fe segments are used for substrate coupling of nanobarcodes and as ligand-free nano-segments and Au segments for ligand coating while maintaining both nanoscale (local) and macroscale (total) ligand density constant in all groups. Low nano-ligand frequency in the same sequences and terminally sequenced nano-ligands at the same frequency independently facilitate focal adhesion and mechanosensing of stem cells, which are collectively effective both in vitro and in vivo, thereby inducing stem cell differentiation. The Fe/RGD-Au nanobarcode implants exhibit high stability and no local and systemic toxicity in various tissues and organs in vivo. This work sheds novel insight into designing biomaterials with heterogeneous nano-ligand sequences at terminal sides and/or low frequency to facilitate cellular adhesion. Tuning the electrodeposition conditions can allow synthesis of unlimited combinations of ligand nano-sequences and frequencies, magnetic elements, and bioactive ligands to remotely regulate numerous host cells in vivo.",

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author = "Sunhong Min and Jeon, {Yoo Sang} and Jung, {Hee Joon} and Chandra Khatua and Na Li and Gunhyu Bae and Hyojun Choi and Hyunsik Hong and Shin, {Jeong Eun} and Ko, {Min Jun} and Ko, {Han Seok} and Indong Jun and Fu, {Hong En} and Kim, {Seung Hyun} and Ramar Thangam and Song, {Jae Jun} and Dravid, {Vinayak P.} and Kim, {Young Keun} and Heemin Kang",

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Min, S, Jeon, YS, Jung, HJ, Khatua, C, Li, N, Bae, G, Choi, H, Hong, H, Shin, JE, Ko, MJ, Ko, HS, Jun, I, Fu, HE, Kim, SH, Thangam, R, Song, JJ, Dravid, VP, Kim, YK & Kang, H 2020, 'Independent Tuning of Nano-Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells', Advanced Materials, vol. 32, no. 40, 2004300. https://doi.org/10.1002/adma.202004300

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AU - Min, Sunhong

AU - Jeon, Yoo Sang

AU - Jung, Hee Joon

AU - Khatua, Chandra

AU - Li, Na

AU - Bae, Gunhyu

AU - Choi, Hyojun

AU - Hong, Hyunsik

AU - Shin, Jeong Eun

AU - Ko, Min Jun

AU - Ko, Han Seok

AU - Jun, Indong

AU - Fu, Hong En

AU - Kim, Seung Hyun

AU - Thangam, Ramar

AU - Song, Jae Jun

AU - Dravid, Vinayak P.

AU - Kim, Young Keun

AU - Kang, Heemin

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Independent Tuning of Nano-Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells

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