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A Versatile Microfluidic Platform for Extravasation Studies Based on DNA Origami-Cell Interactions.

Miguel García-Chamé1, Parvesh Wadhwani2, Juliana Pfeifer3

  • 1Karlsruhe Institute of Technology (KIT), Institute for Biological Interfaces 1 (IBG 1), Hermann-von-Helmholtz-Platz, 76344, Eggenstein-Leopoldshafen, Germany.

Angewandte Chemie (International Ed. in English)
|April 30, 2024
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Summary

This study introduces a new microfluidic device to observe cancer cell extravasation. It reveals how adhesion peptide details on DNA nanostructures influence cancer cell metastasis.

Keywords:
DNA structurescancerextravasationintegrinsmicrofluidics

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Cancer Research

Background:

  • Circulating tumor cells (CTCs) extravasation is key to metastasis, but difficult to study.
  • Integrins on CTCs regulate extravasation, yet current models have limitations.
  • Understanding cancer cell adhesion is vital for developing anti-metastatic therapies.

Purpose of the Study:

  • To develop a novel microfluidic device for studying cancer cell extravasation.
  • To investigate the role of integrin-specific adhesion in cancer cell transmigration.
  • To analyze how nanoscale patterns of adhesion peptides affect extravasation.

Main Methods:

  • A microfluidic device with a porous membrane functionalized with DNA origami nanostructures (DONs).
  • DONs display nanoscale patterns of adhesion peptides to mimic the endothelial barrier.
  • 3D confocal imaging to visualize cancer cell transmigration under physiological flow conditions.

Main Results:

  • The device allows study of integrin-specific adhesion independently.
  • Cancer cell extravasation (MDA-MB-231) is sensitive to peptide type, distance, and density on DONs.
  • Combined RGD and IDS peptides did not enhance extravasation synergistically.

Conclusions:

  • The microfluidic system provides a powerful tool for studying cancer cell extravasation.
  • Nanoscale control over adhesion peptides influences cancer cell transmigration.
  • Integrin-mediated adhesion is complex and not always additive in promoting metastasis.