A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility

Synthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self‐propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven...

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Veröffentlicht in:Angewandte Chemie International Edition 2021-12, Vol.60 (50), p.26087-26095
Hauptverfasser: Li, Hao, Gao, Jing, Cao, Lei, Xie, Xuan, Fan, Jiahui, Wang, Hongda, Wang, Hong‐Hui, Nie, Zhou
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container_issue 50
container_start_page 26087
container_title Angewandte Chemie International Edition
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creator Li, Hao
Gao, Jing
Cao, Lei
Xie, Xuan
Fan, Jiahui
Wang, Hongda
Wang, Hong‐Hui
Nie, Zhou
description Synthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self‐propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane‐floating cell‐surface receptors in a stochastic manner and simultaneously trigger the receptor‐dimerization to activate downstream signaling for cell motility. The cell membrane‐associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell‐driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution. A DNA molecular robot that autonomously walks on the cell membrane to drive the cell motility has been developed. The DNA robot could move stepwise on the membrane‐floating cell‐surface receptors in a stochastic manner and simultaneously trigger the receptor‐dimerization to activate downstream signal pathway regulation of desired cellular behavior.
doi_str_mv 10.1002/anie.202108210
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However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self‐propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane‐floating cell‐surface receptors in a stochastic manner and simultaneously trigger the receptor‐dimerization to activate downstream signaling for cell motility. The cell membrane‐associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell‐driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution. A DNA molecular robot that autonomously walks on the cell membrane to drive the cell motility has been developed. 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The DNA robot could move stepwise on the membrane‐floating cell‐surface receptors in a stochastic manner and simultaneously trigger the receptor‐dimerization to activate downstream signal pathway regulation of desired cellular behavior.</description><subject>A549 Cells</subject><subject>AKT protein</subject><subject>Catalytic activity</subject><subject>Cell adhesion &amp; migration</subject><subject>cell manipulation</subject><subject>Cell Membrane - chemistry</subject><subject>Cell Membrane - metabolism</subject><subject>Cell membranes</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell surface</subject><subject>Cytoskeleton</subject><subject>Deoxyribonucleic acid</subject><subject>Dimerization</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>DNA - metabolism</subject><subject>DNA robots</subject><subject>DNA walkers</subject><subject>DNA, Catalytic - metabolism</subject><subject>DNAzymes</subject><subject>Humans</subject><subject>membrane receptors</subject><subject>Membranes</subject><subject>Motility</subject><subject>Receptors</subject><subject>Robot dynamics</subject><subject>Robots</subject><subject>Signaling</subject><subject>Stochasticity</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtLxDAQxoMorq-rRwl48dI1rzbJseyuD_ABooinkGZTrKaNJq2y_71ZVlfw4mGYYeY3Hx8fAIcYjTFC5FR3jR0TRDASqTbADs4JzijndDPNjNKMixyPwG6ML4kXAhXbYEQZk6iQdAc8lXB6U8Jr76wZnA7wzle-h_2z7mE59L7zrR-iW8BH7V4j9F06WTixzsFr21ZBdxb2Hk5D8_Gz9n3jmn6xD7Zq7aI9-O574OFsdj-5yK5uzy8n5VVmKKco03mNTS2F1LIS2hBqGOI5IVjn1lRmLjkXCCPKjUTUyjlhBamYKOYCM1bVlO6Bk5XuW_Dvg429aptokpNkLVlXJOcIY0x5ntDjP-iLH0KX3ClSICplLgqWqPGKMsHHGGyt3kLT6rBQGKll6GoZulqHnh6OvmWHqrXzNf6TcgLkCvhsnF38I6fKm8vZr_gXxRiLdA</recordid><startdate>20211206</startdate><enddate>20211206</enddate><creator>Li, Hao</creator><creator>Gao, Jing</creator><creator>Cao, Lei</creator><creator>Xie, Xuan</creator><creator>Fan, Jiahui</creator><creator>Wang, Hongda</creator><creator>Wang, Hong‐Hui</creator><creator>Nie, Zhou</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9864-2965</orcidid></search><sort><creationdate>20211206</creationdate><title>A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility</title><author>Li, Hao ; 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subjects A549 Cells
AKT protein
Catalytic activity
Cell adhesion & migration
cell manipulation
Cell Membrane - chemistry
Cell Membrane - metabolism
Cell membranes
Cell migration
Cell Movement
Cell surface
Cytoskeleton
Deoxyribonucleic acid
Dimerization
DNA
DNA - chemistry
DNA - metabolism
DNA robots
DNA walkers
DNA, Catalytic - metabolism
DNAzymes
Humans
membrane receptors
Membranes
Motility
Receptors
Robot dynamics
Robots
Signaling
Stochasticity
title A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility
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