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Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice
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, availab...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159096/ https://www.ncbi.nlm.nih.gov/pubmed/35733880 http://dx.doi.org/10.1039/d2sc00371f |
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author | Su, Yingying Chen, Xiaoqing Wang, Hui Sun, Lele Xu, Ying Li, Di |
author_facet | Su, Yingying Chen, Xiaoqing Wang, Hui Sun, Lele Xu, Ying Li, Di |
author_sort | Su, Yingying |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9159096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-91590962022-06-21 Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice Su, Yingying Chen, Xiaoqing Wang, Hui Sun, Lele Xu, Ying Li, Di Chem Sci Chemistry 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. The Royal Society of Chemistry 2022-05-02 /pmc/articles/PMC9159096/ /pubmed/35733880 http://dx.doi.org/10.1039/d2sc00371f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Su, Yingying Chen, Xiaoqing Wang, Hui Sun, Lele Xu, Ying Li, Di Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice |
title | Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice |
title_full | Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice |
title_fullStr | Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice |
title_full_unstemmed | Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice |
title_short | Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice |
title_sort | enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive dna nanodevice |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159096/ https://www.ncbi.nlm.nih.gov/pubmed/35733880 http://dx.doi.org/10.1039/d2sc00371f |
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