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Tuning Epithelial Cell-Cell Adhesion and Collective Dynamics with Functional DNA-E-Cadherin Hybrid Linkers
Max Planck Inst Med Res, Biophys Engn Grp, D-69120 Heidelberg, Germany.;Max Planck Inst Med Res, Dept Cellular Biophys, Growth Factor Mechanobiol Grp, D-69120 Heidelberg, Germany.;CNRS, Inst Jacques Monod, F-75013 Paris, France.;Univ Paris, F-75013 Paris, France..ORCID iD: 0000-0003-3714-5636
Max Planck Inst Med Res, Dept Cellular Biophys, Growth Factor Mechanobiol Grp, D-69120 Heidelberg, Germany..
Max Planck Inst Med Res, Biophys Engn Grp, D-69120 Heidelberg, Germany.;Max Planck Inst Med Res, Dept Cellular Biophys, Growth Factor Mechanobiol Grp, D-69120 Heidelberg, Germany..
Max Planck Inst Med Res, Dept Cellular Biophys, Growth Factor Mechanobiol Grp, D-69120 Heidelberg, Germany.ORCID iD: 0000-0002-9490-7070
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2022 (English)In: Nano Letters, ISSN 1530-6984, E-ISSN 1530-6992, Vol. 22, no 1, p. 302-310Article in journal (Refereed) Published
Abstract [en]

The binding strength between epithelial cells is crucial for tissue integrity, signal transduction and collective cell dynamics. However, there is no experimental approach to precisely modulate cell-cell adhesion strength at the cellular and molecular level. Here, we establish DNA nanotechnology as a tool to control cell-cell adhesion of epithelial cells. We designed a DNA-E-cadherin hybrid system consisting of complementary DNA strands covalently bound to a truncated E-cadherin with a modified extracellular domain. DNA sequence design allows to tune the DNA-E-cadherin hybrid molecular binding strength, while retaining its cytosolic interactions and downstream signaling capabilities. The DNA-E-cadherin hybrid facilitates strong and reversible cell-cell adhesion in E-cadherin deficient cells by forming mechanotransducive adherens junctions. We assess the direct influence of cell-cell adhesion strength on intracellular signaling and collective cell dynamics. This highlights the scope of DNA nanotechnology as a precision technology to study and engineer cell collectives.

Place, publisher, year, edition, pages
American Chemical Society (ACS) , 2022. Vol. 22, no 1, p. 302-310
Keywords [en]
cell-cell adhesion strength, E-cadherin, DNA nanotechnology, adherens junction, epithelial cells, collective migration, DNA-protein hybrid, mechanotransduction
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-310643DOI: 10.1021/acs.nanolett.1c03780ISI: 000769996700041PubMedID: 34939414Scopus ID: 2-s2.0-85122294937OAI: oai:DiVA.org:kth-310643DiVA, id: diva2:1651220
Note

QC 20230612

Available from: 2022-04-11 Created: 2022-04-11 Last updated: 2023-09-25Bibliographically approved

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Ollech, Dirk

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Schoenit, AndreasOllech, DirkCavalcanti-Adam, Elisabetta Ada
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