High‐Throughput DNA Tensioner Platform for Interrogating Mechanical Heterogeneity of Single Living Cells
Xinxin Hang, Shiqi He, Zaizai Dong, Yun Li, Zheng Huang, Yanruo Zhang, Hong Sun, Long Lin, Hu Li, Yang Wang, Bing Liu, Nan Wu, Tianling Ren, Yubo Fan, Jizhong Lou, Ruiguo Yang, Lan Jiang, Lingqian Chang
Abstract
Cell mechanical forces play fundamental roles in regulating cellular responses to environmental stimulations. The shortcomings of conventional methods, including force resolution and cellular throughput, make them less accessible to mechanical heterogeneity at the single-cell level. Here, a DNA tensioner platform is introduced with high throughput (>10 000 cells per chip) and pN-level resolution. A microfluidic-based cell array is trapped on "hairpin-structured" DNA tensioners that enable transformation of the mechanical information of living cells into fluorescence signals. By using the platform, one can identify enhanced mechanical forces of drug-resistant cells as compared to their drug-sensitive counterparts, and mechanical differences between metastatic tumor cells in pleural effusion and nonmetastatic histiocytes. Further genetic analysis traces two genes, VEGFA and MINK1, that may play deterministic roles in regulating mechanical heterogeneities. In view of the ubiquity of cells' mechanical forces in the extracellular microenvironment (ECM), this platform shows wide potential to establish links of cellular mechanical heterogeneity to genetic heterogeneity.