基于 DNA 的单分子力传感器，用于表征癌细胞中侵袭伪足形成和成熟所需的 α5β1 整合素张力,Advanced Functional Materials

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基于 DNA 的单分子力传感器，用于表征癌细胞中侵袭伪足形成和成熟所需的 α5β1 整合素张力
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2022-04-24 , DOI: 10.1002/adfm.202110637
Kyung Ah Kim ₁ , Srivithya Vellampatti ₁ , Sun Ha Hwang ₁ , Byoung Choul Kim ₁

Affiliation

侵袭伪足通过产生机械力和分泌蛋白水解酶参与癌症侵袭。据推测，施加于整合素的物理力，尤其是 α ₅ β ₁整合素，与侵袭足力的产生和侵袭足的突出活动密切相关；然而，它们的机械关系仍然难以捉摸。在这里，开发了一种新的基于脱氧核糖核酸的力探针，用于绘制 α ₅ β ₁具有单分子精度的整合素张力。使用该探针，研究了取决于整合素类型和张力的侵袭伪足的形成和成熟。此外, 对整合素张力图进行时空分析, 以测量整合素张力和侵袭力在侵袭伪足发育的每个阶段的变化。因此，发现超过 40 pN 的 α ₅ β _{1整合素张力不仅对粘附至关重要，而且对侵袭伪足的成熟也至关重要，最终导致通过 α}₅ β ₁产生大于 100 pN 的强侵袭力。具有肌动球蛋白收缩性的整合素-配体复合物。这种侵袭伪足形成和机械激活的生物物理机制可能为癌症侵袭和转移提供新的见解。

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DNA-Based Single Molecule Force Sensor For Characterization of α5β1 Integrin Tension Required for Invadopodia Formation and Maturation in Cancer Cells

Invadopodia are involved in cancer invasion by generating mechanical forces and secreting proteolytic enzymes. It is hypothesized that physical forces applied to integrin, especially α₅β₁ integrin, are strongly associated with the generation of invadopodial forces and protrusive activity of invadopodia; however, their mechanical relationship remains elusive. Here, a new deoxyribonucleic acid-based force probe is developed for mapping α₅β₁ integrin tension with single-molecule precision. Using this probe, the formation and maturation of invadopodia depending on integrin type and tension are investigated. In addition, the spatio-temporal analysis of the integrin tension map is performed to measure changes in integrin tension and invadopodial force in each stage of invadopodia development. Consequently, it is found that α₅β₁ integrin tension above 40 pN is critical not only for adhesion but also for the maturation of invadopodia, eventually leading to the generation of a strong invadopodial force greater than 100 pN through α₅β₁ integrin-ligand complexes with actomyosin contractility. This biophysical mechanism underlying the invadopodia formation and mechanical activation may provide new insights into cancer invasion and metastasis.

更新日期：2022-04-24

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