한빛사논문
한국과학기술연구원
Sungkyu Lee a,1, Jounghyun Yoo b,1, Gunhyu Bae a, Ramar Thangam a, Jeongyun Heo b, Jung Yeon Park c, Honghwan Choi b,c, Chowon Kim a, Jusung An d, Jungryun Kim d, Kwang Rok Mun e, Seungyong Shin e, Kunyu Zhang f, Pengchao Zhao f, Yuri Kim a, Nayeon Kang a, Seong-Beom Han c, Dahee Kim a, Jiwon Yoon b, Misun Kang e, Jihwan Kim b,c, Letao Yang g, Solmaz Karamikamkar h, Jinjoo Kim h, Yangzhi Zhu h, Alireza Hassani Najafabadi h, Guosheng Song i, Dong-Hwee Kim c, Ki-Bum Lee g, Soong Ju Oh a, Hyun-Do Jung j,s, Hyun-Cheol Song k,l, Woo Young Jang m, Liming Bian f, Zhiqin Chu n, Juyoung Yoon o, Jong Seung Kim d, Yu Shrike Zhang p, Yongju Kim c, Ho Seong Jang e,q, Sehoon Kim b,c, Heemin Kang a,r
aDepartment of Materials Science and Engineering, Korea University, Seoul, 02841, Republic of Korea
bChemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
cKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea
dDepartment of Chemistry, Korea University, Seoul, 02841, Republic of Korea
eMaterials Architecturing Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
fSchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 511442, China
gDepartment of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, 08854, USA
hTerasaki Institute for Biomedical Innovation, Los Angeles, CA, 90064, USA
iState Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China
jDepartment of Biomedical-Chemical Engineering, The Catholic University of Korea, Gyeonggi-do, 14662, Republic of Korea
kElectronic Materials Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
lKIST-SKKU Carbon-Neutral Research Center, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
mDepartment of Orthopedic Surgery, Korea University Anam Hospital, Seoul, 02841, Republic of Korea
nDepartment of Electrical and Electronic Engineering and Joint Appointment with School of Biomedical Sciences, The University of Hong Kong, Hong Kong, 518057, China
oDepartment of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea
pDivision of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Cambridge, MA, 02139, USA
qDivision of Nano & Information Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea
rCollege of Medicine, Korea University, Seoul, 02841, Republic of Korea
sDivision of Materials Science and Engineering, Hanyang University, Seoul, 04763, Republic of Korea
1These authors contribute equally to this work.
Corresponding authors: Ho Seong Jang, Sehoon Kim, Heemin Kang
Abstract
Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of “closely nanospaced” ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with “closely nanospaced” ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of “distantly nanospaced” ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.
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