4.8 Article

A reversible shearing DNA probe for visualizing mechanically strong receptors in living cells

Journal

NATURE CELL BIOLOGY
Volume 23, Issue 6, Pages 642-+

Publisher

NATURE RESEARCH
DOI: 10.1038/s41556-021-00691-0

Keywords

-

Categories

Funding

  1. National Natural Science Foundation of China [21775115, 32071305, 31670760, 11704286, 11674403]
  2. Wuhan University
  3. Fundamental Research Funds for the Central Universities [2042018kf02]

Ask authors/readers for more resources

Researchers developed a reversible DNA-based tension probe for quantifying weak forces between cells, which will help to better understand the molecular mechanisms of mechanobiology.
Li et al. develop reversible shearing DNA-based tension probes to quantify molecular piconewton-scale forces, estimate the number of mechanically active receptors with single-molecule sensitivity and study mechanisms of force transduction in live cells. In the last decade, DNA-based tension sensors have made significant contributions to the study of the importance of mechanical forces in many biological systems. Albeit successful, one shortcoming of these techniques is their inability to reversibly measure receptor forces in a higher regime (that is, >20 pN), which limits our understanding of the molecular details of mechanochemical transduction in living cells. Here, we developed a reversible shearing DNA-based tension probe (RSDTP) for probing molecular piconewton-scale forces between 4 and 60 pN transmitted by cells. Using these probes, we can easily distinguish the differences in force-bearing integrins without perturbing adhesion biology and reveal that a strong force-bearing integrin cluster can serve as a 'mechanical pivot' to maintain focal adhesion architecture and facilitate its maturation. The benefits of the RSDTP include a high dynamic range, reversibility and single-molecule sensitivity, all of which will facilitate a better understanding of the molecular mechanisms of mechanobiology.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemistry & Molecular Biology

The Golgi microtubules regulate single cell durotaxis

Yingxue Rong, Wenzhong Yang, Huiwen Hao, Wenxu Wang, Shaozhen Lin, Peng Shi, Yuxing Huang, Bo Li, Yujie Sun, Zheng Liu, Congying Wu

Summary: Our research reveals the crucial role of Golgi microtubules in single cell durotactic migration, influencing the dynamics of leading edge focal adhesions and showing that Golgi positioning responds to external mechanical cues. This study uncovers the cytoskeletal underpinning of single cell durotaxis, proposing a model where the Golgi-nucleus axis serves as both a compass and a steering wheel for cell directionality.

EMBO REPORTS (2021)

Article Cell Biology

Mrc1-Dependent Chromatin Compaction Represses DNA Double-Stranded Break Repair by Homologous Recombination Upon Replication Stress

Poyuan Xing, Yang Dong, Jingyu Zhao, Zhou Zhou, Zhao Li, Yu Wang, Mengfei Li, Xinghua Zhang, Xuefeng Chen

Summary: The study demonstrates that replication stress suppresses resection pathways mediated by Sgs1/Dna2 and Exo1, leading to disruption in DNA replication and repair. Mrc1 plays a crucial role in inhibiting DSB end resection through regulating chromatin compaction to limit access of HR proteins.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Article Chemistry, Analytical

Exploring Integrin-Mediated Force Transmission during Confined Cell Migration by DNA-Based Tension Probes

Liang Wang, Wei Chen, Hongyun Li, Chaohui Xiong, Feng Sun, Xiaoqing Liu, Yuru Hu, Wenxu Wang, Wenqun Zhong, Zheng Liu

Summary: Mechanical forces have profound effects on cell morphology and migration in a two-dimensional environment. However, the mechanism by which cells migrate in a confined three-dimensional environment is unclear. This study presents a method of fabricating microfluidic chips with DNA-based tension probes to measure force exerted during confined cell migration. The results show that cells exert less force and have increasingly transient interactions in confined spaces.

ANALYTICAL CHEMISTRY (2022)

Article Physics, Multidisciplinary

Multivalent Cations Reverse the Twist-Stretch Coupling of RNA

Xiao-Wei Qiang, Chen Zhang, Hai-Long Dong, Fu-Jia Tian, Hang Fu, Ya-Jun Yang, Liang Dai, Xing-Hua Zhang, Zhi-Jie Tan

Summary: It has been discovered that both RNA and DNA can change their twist angles through twist-stretch coupling when stretched. The coupling is positive for RNA and negative for DNA. Magnetic tweezers experiments have shown that the coupling of RNA can be reversed from positive to negative by multivalent cations. Molecular dynamics simulations have provided a unified mechanism for the couplings of both RNA and DNA.

PHYSICAL REVIEW LETTERS (2022)

Article Multidisciplinary Sciences

Twist-diameter coupling drives DNA twist changes with salt and temperature

Chen Zhang, Fujia Tian, Ying Lu, Bing Yuan, Zhi-Jie Tan, Xing-Hua Zhang, Liang Dai

Summary: DNA deformations can occur upon environmental changes, and an increase in salt concentration leads to DNA overwinding. Our magnetic tweezers experiments and simulations demonstrate that the twist change induced by salt can be quantitatively explained by the screening of electrostatic repulsion and the coupling between twist and DNA diameter. We determine the coupling constant and predict the temperature dependence of DNA twist, finding that the twist-diameter coupling is a common driving force for salt- and temperature-induced DNA twist changes.

SCIENCE ADVANCES (2022)

Article Biochemistry & Molecular Biology

5-Methyl-cytosine stabilizes DNA but hinders DNA hybridization revealed by magnetic tweezers and simulations

Xiao-Cong Zhao, Hai-Long Dong, Xiao-Lu Li, Hong-Yu Yang, Xue-Feng Chen, Liang Dai, Wen-Qiang Wu, Zhi-Jie Tan, Xing-Hua Zhang

Summary: 5-Methyl-cytosine (5mC) is one of the most important DNA modifications, playing versatile biological roles. This study reveals that 5mC kinetically hinders DNA hybridization due to steric effects, leading to high energy barriers.

NUCLEIC ACIDS RESEARCH (2022)

Article Biochemistry & Molecular Biology

Proper RPA acetylation promotes accurate DNA replication and repair

Xiaoli Gan, Yueyue Zhang, Donghao Jiang, Jingyao Shi, Han Zhao, Chengyu Xie, Yanyan Wang, Jingyan Xu, Xinghua Zhang, Gang Cai, Hailong Wang, Jun Huang, Xuefeng Chen

Summary: The acetylation and deacetylation of RPA are crucial for regulating its function in DNA replication and repair processes. RPA is acetylated by NuA4 upon DNA damage, and mutations in RPA acetylation lead to spontaneous mutations and impaired DNA repair. Proper acetylation and deacetylation of RPA are necessary for its normal nuclear localization and ssDNA binding ability. These findings suggest that timely acetylation and deacetylation of RPA are conserved mechanisms promoting high-fidelity replication and repair in eukaryotes.

NUCLEIC ACIDS RESEARCH (2023)

Article Multidisciplinary Sciences

Universality in RNA and DNA deformations induced by salt, temperature change, stretching force, and protein binding

Fu-Jia Tian, Chen Zhang, Erchi Zhou, Hai-Long Dong, Zhi-Jie Tan, Xing-Hua Zhang, Liang Dai, Taekjip Ha

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

Article Chemistry, Multidisciplinary

Exploring Mechanical Responses of Cells to Geometric Information Using Micropatterned DNA-Based Molecular Tension Probes

Feng Sun, Hongyun Li, Yuru Hu, Mengsheng Zhang, Wenxu Wang, Wei Chen, Zheng Liu

Summary: The geometric shape of a cell is influenced by the cytoskeleton and cell-extracellular matrix interactions. A combination of single-cell micropatterning and molecular tension fluorescence microscopy allows studying the mechanical properties of cells with prescribed geometries. Curvature is found to be a key geometric cue for cells to differentiate shapes, and the integrin subunit beta(1) plays a critical role in detecting geometric information.

ACS NANO (2023)

Article Biochemistry & Molecular Biology

A mutation-sensitive, multiplexed and amplification-free detection of nucleic acids by stretching single-molecule tandem hairpin probes

Ya-Jun Yang, Hang Fu, Xiao-Lu Li, Hong-Yu Yang, Er-Chi Zhou, Cheng-Yu Xie, Shu-Wen Wu, Fan He, Yan Zhang, Xing-Hua Zhang

Summary: A single-molecule nucleic acid detection assay called THREF was developed using multiplexed magnetic tweezers. THREF can detect DNA and RNA sequences at femtomolar concentrations within 30 min, monitor multiple probes, quantify miR-122 expression, discriminate SNVs, and save costs. It has the advantages of high sensitivity, ultra-specificity, multiplexing, reusability, sample hands-free, and robustness.

NUCLEIC ACIDS RESEARCH (2023)

No Data Available