이건희 (고려대학교, 현 Johns Hopkins University) | 한빛사논문 > 한빛사

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이건희Geonhui Lee

고려대학교, 현 Johns Hopkins University

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Adv. Sci., Feb 04 2024, | https://doi.org/10.1002/advs.202306497 Selective Suppression of Integrin-Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration

Seong-Beom Han ¹, Geonhui Lee¹, Daesan Kim ¹, Jeong-Ki Kim¹, In-San Kim ^1,2, Hae-Won Kim ^3,4, Dong-Hwee Kim^1,2,5

¹KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea.

²Biomedical Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.

³Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea.

⁴Department of Biomaterials Science in College of Dentistry & Department of Nanobiomedical Science in Graduate School, Dankook University, Cheonan, 31116, Republic of Korea.

⁵Department of Integrative Energy Engineering, College of Engineering, Korea University, Seoul, 02841, Republic of Korea.

S.B.H. and G.L. contributed equally to this work.

CORRESPONDING AUTHOR : Dong-Hwee Kim

Abstract

Cell migration interacting with continuously changing microenvironment, is one of the most essential cellular functions, participating in embryonic development, wound repair, immune response, and cancer metastasis. The migration process is finely tuned by integrin-mediated binding to ligand molecules. Although numerous biochemical pathways orchestrating cell adhesion and motility are identified, how subcellular forces between the cell and extracellular matrix regulate intracellular signaling for cell migration remains unclear. Here, it is showed that a molecular binding force across integrin subunits determines directional migration by regulating tension-dependent focal contact formation and focal adhesion kinase phosphorylation. Molecular binding strength between integrin α _v β ₃ and fibronectin is precisely manipulated by developing molecular tension probes that control the mechanical tolerance applied to cell-substrate interfaces. This data reveals that integrin-mediated molecular binding force reduction suppresses cell spreading and focal adhesion formation, attenuating the focal adhesion kinase (FAK) phosphorylation that regulates the persistence of cell migration. These results further demonstrate that manipulating subcellular binding forces at the molecular level can recapitulate differential cell migration in response to changes of substrate rigidity that determines the physical condition of extracellular microenvironment. Novel insights is provided into the subcellular mechanics behind global mechanical adaptation of the cell to surrounding tissue environments featuring distinct biophysical signatures.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-06)
연구진국내 연구진
분야 생명과학 > 세포생물학

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