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      Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice†

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      Chemical Science
      The Royal Society of Chemistry

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          Abstract

          Phase separation in cell membranes promotes the assembly of transmembrane receptors to initiate signal transduction in response to environmental cues. Many cellular behaviors are manipulated by promoting membrane phase separation through binding to multivalent extracellular ligands. However, available extracellular molecule tools that enable manipulating the clustering of transmembrane receptors in a controllable manner are rare. In the present study, we report a DNA nanodevice that enhances membrane phase separation through the clustering of dynamic lipid rafts. This DNA nanodevice is anchored in the lipid raft region of the cell membrane and initiated by ATP. In a tumor microenvironment, this device could be activated to form a long DNA duplex on the cell membrane, which not only enhances membrane phase separation, but also blocks the interaction between the transmembrane surface adhesion receptor and extracellular matrix, leading to reduced migration. We demonstrate that the ATP-activated DNA nanodevice could inhibit cancer cell migration both in vitro and in vivo. The concept of using DNA to regulate membrane phase separation provides new possibilities for manipulating versatile cell functions through rational design of functional DNA structures.

          Abstract

          A DNA nanodevice is developed to enhance the cell membrane phase separation in a tumor microenvironment to weaken the formation of focal adhesion. As a result, the migration of cancer cells is inhibited both in vitro and in vivo.

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          Author and article information

          Journal
          Chem Sci
          Chem Sci
          SC
          CSHCBM
          Chemical Science
          The Royal Society of Chemistry
          2041-6520
          2041-6539
          2 May 2022
          1 June 2022
          2 May 2022
          : 13
          : 21
          : 6303-6308
          Affiliations
          [a] School of Chemistry and Molecular Engineering, East China Normal University 200241 Shanghai China dli@ 123456chem.ecnu.edu.cn
          [b] School of Life Science, Shanghai University Shanghai 200444 China
          [c] Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiao-Tong University School of Medicine Shanghai 200025 China
          Author information
          https://orcid.org/0000-0003-1674-0110
          Article
          d2sc00371f
          10.1039/d2sc00371f
          9159096
          35733880
          d377f3ea-6cef-4083-8f62-de9c6bf7cdfe
          This journal is © The Royal Society of Chemistry
          History
          : 20 January 2022
          : 26 April 2022
          Page count
          Pages: 6
          Funding
          Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;
          Award ID: 21874046
          Funded by: Science and Technology Commission of Shanghai Municipality, doi 10.13039/501100003399;
          Award ID: 19JC1411800
          Funded by: Chinese Academy of Sciences, doi 10.13039/501100002367;
          Award ID: ZDBS-LY-JSC010
          Funded by: East China Normal University, doi 10.13039/501100004106;
          Award ID: 011
          Funded by: Fundamental Research Funds for the Central Universities, doi 10.13039/501100012226;
          Award ID: Unassigned
          Categories
          Chemistry
          Custom metadata
          Paginated Article

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