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Selectins01:25

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Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
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Direct visualization of superselective colloid-surface binding mediated by multivalent interactions.

Christine Linne1,2, Daniele Visco3,4, Stefano Angioletti-Uberti3,4

  • 1Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden Institute of Physics, 2300 RA Leiden, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America
|September 1, 2021
PubMed
Summary
This summary is machine-generated.

This study introduces a novel multivalent model system using DNA linkers on colloidal particles to achieve superselective targeting. The system reveals how ligand-receptor dynamics influence binding, offering insights into cell recognition and drug delivery.

Keywords:
DNA-coated colloidsbinding kineticsmultivalent interactionssuperselectivitysurface adhesion

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Materials Science

Background:

  • Accurate cell differentiation based on receptor density is vital for biological processes like cell recognition and drug delivery.
  • Multivalent interactions are key to achieving high selectivity ('superselectivity') in these processes.
  • A controlled experimental system for quantitative, ligand-receptor level measurements is currently lacking.

Purpose of the Study:

  • To develop and characterize a versatile multivalent model system for studying superselectivity.
  • To quantitatively measure ligand-receptor interactions at the molecular level.
  • To elucidate the dynamic mechanisms underlying multivalent binding and superselectivity.

Main Methods:

  • Development of a model system using colloidal particles with surface-mobile DNA linkers.
  • Functionalization of a target surface with complementary mobile DNA linkers.
  • Utilizing light microscopy and Förster Resonance Energy Transfer (FRET) to observe binding dynamics.

Main Results:

  • Demonstrated superselective targeting of functionalized surfaces by DNA-linker-equipped colloidal particles.
  • Observed a nonlinear relationship between binding probability and ligand/receptor concentration.
  • Found increased sensitivity with weaker ligand-receptor interactions and confirmed the influence of binding reversibility timescale on superselectivity.

Conclusions:

  • The novel multivalent model system provides unprecedented, dynamic insights into ligand-receptor interactions.
  • This system enables quantitative study of molecular interactions at fluidic membrane interfaces.
  • Findings pave the way for future research on spatial-temporal dynamics in colloid-surface binding and its biological implications.