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首页> 外文期刊>Advanced functional materials >DNA-Based Single Molecule Force Sensor For Characterization of α_5β_1 Integrin Tension Required for Invadopodia Formation and Maturation in Cancer Cells
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DNA-Based Single Molecule Force Sensor For Characterization of α_5β_1 Integrin Tension Required for Invadopodia Formation and Maturation in Cancer Cells

机译：DNA-Based Single Molecule Force Sensor For Characterization of α_5β_1 Integrin Tension Required for Invadopodia Formation and Maturation in Cancer Cells

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摘要

Invadopodia are involved in cancer invasion by generating mechanicalforces and secreting proteolytic enzymes. It is hypothesized that physicalforces applied to integrin, especially α_5β_1 integrin, are strongly associatedwith the generation of invadopodial forces and protrusive activity of invadopodia;however, their mechanical relationship remains elusive. Here, anew deoxyribonucleic acid-based force probe is developed for mapping α_5β_1integrin tension with single-molecule precision. Using this probe, the formationand maturation of invadopodia depending on integrin type and tensionare investigated. In addition, the spatio-temporal analysis of the integrintension map is performed to measure changes in integrin tension and invadopodialforce in each stage of invadopodia development. Consequently, it isfound that α_5β_1 integrin tension above 40 pN is critical not only for adhesionbut also for the maturation of invadopodia, eventually leading to the generationof a strong invadopodial force greater than 100 pN through α_5β_1 integrinligandcomplexes with actomyosin contractility. This biophysical mechanismunderlying the invadopodia formation and mechanical activation may providenew insights into cancer invasion and metastasis.

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