Spatially resolved single-molecule profiling of microRNAs in migrating cells driven by microconfinement

• Published in: Chemical science (Cambridge) Vol. 13; no. 37; pp. 11197 - 1124
• Main Authors: Fan, Zihui, Li, Bin, Wang, Ya-Jun, Huang, Xuedong, Li, Binxiao, Wang, Shurong, Liu, Yixin, Liu, Yan-Jun, Liu, Baohong
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 28.09.2022; The Royal Society of Chemistry
• Subjects: Biomimetics; Biomolecules; Cancer; Cell adhesion & migration; Chemistry; High resolution; Medical imaging; MicroRNAs; Regulatory mechanisms (biology); Spatial distribution
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d2sc04132d

Cancer cells utilize a range of migration modes to navigate through a confined tissue microenvironment in vivo , while regulatory roles of key microRNAs (miRNAs) remain unclear. Precisely engineered microconfinement and the high spatial-resolution imaging strategy offer a promising avenue for deciphering the molecular mechanisms that drive cell migration. Here, enzyme-free signal-amplification nanoprobes as an effective tool are developed for three-dimensional (3D) high-resolution profiling of key miRNA molecules in single migrating cells, where distinct migration modes are precisely driven by microconfinement-engineered microchips. The constructed nanoprobes exhibit intuitive and ultrasensitive miRNA characterization in vitro by virtue of a single-molecule imaging microscope, and the differential expression and intracellular locations in different cell lines are successfully monitored. Furthermore, 3D spatial distribution of miR-141 at high resolution in flexible phenotypes of migrating cells is reconstructed in the engineered biomimetic microenvironment. The results indicate that miR-141 may be involved in the metastatic transition from a slow to a fast migration state. This work offers a new opportunity for investigating regulatory mechanisms of intracellular key biomolecules during cell migration in biomimetic microenvironments, which may advance in-depth understanding of cancer metastasis in vivo . Spatially resolved profiling of miRNAs was realized in migrating cells using enzyme-free signal-amplification nanoprobes, in which distinct migration modes of single living cells are driven by precisely engineered microchips.