journal article·2022-03

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

Small· Volume 18· Issue 12
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Abstract

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.
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Research context

OpenAlex topics: Cellular Mechanics and Interactions · Microfluidic and Bio-sensing Technologies · Force Microscopy Techniques and Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Biomechanics and Mechanobiology Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering Beihang University No. 37 Xueyuan Road, Haidian District Beijing 100083 China

CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics, and China National Center for Bioinformation Chinese Academy of Sciences No. 1 Beichen West Road, Chaoyang District Beijing 100101 China

Key Laboratory of RNA Biology CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences No. 15 Datun Road, Chaoyang District Beijing 100101 China

Key Laboratory of Carcinogenesis and Translational Research of Ministry of Education Department of Thoracic Surgery II Peking University Cancer Hospital & Institute No. 52 Fucheng Road, Haidian District Beijing 100142 China

Beijing National Research Center for Information Science and Technology (BNRist) Institute of Microelectronics Tsinghua University No. 30 Shuangqing Road, Haidian District Beijing 100084 China

Nebraska Center for Integrated Biomolecular Communication Department of Mechanical and Materials Engineering University of Nebraska‐Lincoln Lincoln NE 68588 USA

College of Future Technology, and Sino‐Danish College University of Chinese Academy of Sciences No. 19(A) Yuquan Road, Shijingshan District Beijing 100049 China

School of Biomedical Engineering Research and Engineering Center of Biomedical Materials Anhui Medical University No. 81 Meishan Road Hefei 230032 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Beijing Municipality · National Key Research and Development Program of China

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