期刊
NANO LETTERS
卷 19, 期 10, 页码 7503-7513出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b03325
关键词
Cell surface receptors; EGFR and integrin; caveolae; cytoskeleton; pN forces; DNA nanodevice (DNA-ND)
类别
资金
- National Key R&D Program of China [2017YFA0700500]
- National Natural Science Foundation of China [21327902, 21635004]
Cell-surface receptors (e.g., EGFR and integrin) and their interactions play determining roles in signal transduction and cytoskeletal activation, which affect cell attachment/detachment, invasion, motility, metastasis (intracellular), and cell-cell signaling. For instance, the interactions between the EGFR and integrin (alpha 6 beta 4) may cause increased mechanical force and shear stress via enhanced cytoskeleton activation. Here, we design a DNA nanodevice (DNA-ND) that can simultaneously target the EGFR and integrin receptors on the caveolae. The piconewton (pN) forces in response to the EGFR-integrin coactivation can be sensed upon the unfolding of the DNA hairpin structure on the side arm of the device via changes of the fluorescence and plasmonic signals. We find that simultaneous activation of EGFR-integrin receptors causes enhanced signal transduction, contractions of the cells, and initiation of the biochemical pathways, thus resulting in a change of the cell division and endocytosis/exocytosis processes that affect the cell proliferation/apoptosis. The DNA-ND further enables us to visualize the cointernalization and degradation of the receptors by lysosomes, providing a novel approach toward bioimaging and mechano-pharmacology.
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