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The Role of Nanoscale Distribution of Fibronectin in the Adhesion of Staphylococcus aureus Studied by Protein Patterning and DNA-PAINT

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  • Heba Khateb
  • ,
  • Rasmus S. Sørensen
  • ,
  • Kimberly Cramer, Max Planck Institute of Biochemistry
  • ,
  • Alexandra S. Eklund, Max Planck Institute of Biochemistry
  • ,
  • Jorgen Kjems
  • Rikke L. Meyer
  • Ralf Jungmann, Max Planck Institute of Biochemistry, Ludwig-Maximilians-Universität
  • ,
  • Duncan S. Sutherland

Staphylococcus aureus is a widespread and highly virulent pathogen that can cause superficial and invasive infections. Interactions between S. aureus surface receptors and the extracellular matrix protein fibronectin mediate the bacterial invasion of host cells and is implicated in the colonization of medical implant surfaces. In this study, we investigate the role of distribution of both fibronectin and cellular receptors on the adhesion of S. aureus to interfaces as a model for primary adhesion at tissue interfaces or biomaterials. We present fibronectin in patches of systematically varied size (100-1000 nm) in a background of protein and bacteria rejecting chemistry based on PLL-g-PEG and studied S. aureus adhesion under flow. We developed a single molecule imaging assay for localizing fibronectin binding receptors on the surface of S. aureus via the super-resolution DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) technique. Our results indicate that S. aureus adhesion to fibronectin biointerfaces is regulated by the size of available ligand patterns, with an adhesion threshold of 300 nm and larger. DNA-PAINT was used to visualize fibronectin binding receptor organization in situ at ∼7 nm localization precision and with a surface density of 38-46 μm-2, revealing that the engagement of two or more receptors is required for strong S. aureus adhesion to fibronectin biointerfaces.

TidsskriftACS Nano
Sider (fra-til)10392-10403
Antal sider12
StatusUdgivet - jul. 2022

Bibliografisk note

Funding Information:
This work was financially supported by the Danmarksgrundforskningsfond center grant DRF135 CellPAT. R.L.M. acknowledges the Carlsberg Foundation grant number CF16-0342 for support.

Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.

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