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강희민
강희민 (Heemin Kang) 저자 이메일 보기
The Chinese University of Hong Kong
조회 304  인쇄하기 주소복사 트위터 공유 페이스북 공유 
라이카코리아는 BRIC 후원기관입니다.
Remote Control of Multimodal Nanoscale Ligand Oscillations Regulates Stem Cell Adhesion and Differentiation
열기 Authors and Affiliations

Abstract
Cellular adhesion is regulated by the dynamic ligation process of surface receptors, such as integrin, to adhesive motifs, such as Arg-Gly-Asp (RGD). Remote control of adhesive ligand presentation using external stimuli is an appealing strategy for the temporal regulation of cell?implant interactions in vivo and was recently demonstrated using photochemical reaction. However, the limited tissue penetration of light potentially hampers the widespread applications of this method in vivo. Here, we present a strategy for modulating the nanoscale oscillations of an integrin ligand simply and solely by adjusting the frequency of an oscillating magnetic field to regulate the adhesion and differentiation of stem cells. A superparamagnetic iron oxide nanoparticle (SPION) was conjugated with the RGD ligand and anchored to a glass substrate by a long flexible poly(ethylene glycol) linker to allow the oscillatory motion of the ligand to be magnetically tuned. In situ magnetic scanning transmission electron microscopy and atomic force microscopy imaging confirmed the nanoscale motion of the substrate-tethered RGD-grafted SPION. Our findings show that ligand oscillations under a low oscillation frequency (0.1 Hz) of the magnetic field promoted integrin?ligand binding and the formation and maturation of focal adhesions and therefore the substrate adhesion of stem cells, while ligands oscillating under high frequency (2 Hz) inhibited integrin ligation and stem cell adhesion, both in vitro and in vivo. Temporal switching of the multimodal ligand oscillations between low- and high-frequency modes reversibly regulated stem cell adhesion. The ligand oscillations further induced the stem cell differentiation and mechanosensing in the same frequency-dependent manner. Our study demonstrates a noninvasive, penetrative, and tunable approach to regulate cellular responses to biomaterials in vivo. Our work not only provides additional insight into the design considerations of biomaterials to control cellular adhesion in vivo but also offers a platform to elucidate the fundamental understanding of the dynamic integrin-ligand binding that regulates the adhesion, differentiation, and mechanotransduction of stem cells.

Keywords: in vivo cell adhesion; integrin ligand oscillations; mesenchymal stem cells; multimodal control; SPION; stem cell differentiation
논문정보
- 형식: Research article
- 게재일: 2017년 08월 (BRIC 등록일 2017-09-07)
- 연구진: 국외연구진
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[GE APAC Fast Trak] 다운스트림 바이오프로세스 개발과정 (DEV2)
사전접수: ~2017.10.13
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장소: 인천시 연수구 송도미래로 9 BRC 2동 2층 GE Healthcare APAC Fast Trak Center
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날짜: 2017.10.11
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