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Engineered molecular sensors for quantifying cell surface crowding.

Sho C Takatori1,2, Sungmin Son1,3, Daniel S W Lee1

  • 1Department of Bioengineering, University of California, Berkeley, CA 94720.

Proceedings of the National Academy of Sciences of the United States of America
|May 15, 2023
PubMed
Summary
This summary is machine-generated.

Cell surface crowding, the dense arrangement of molecules on cell membranes, significantly reduces the binding of macromolecules like antibodies. This study introduces a novel sensor to quantify crowding, revealing its impact on cell interactions and potential as a biomarker.

Keywords:
biophysicscancer cell biologycell surface crowdingglycocalyxplasma membrane

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Area of Science:

  • Biophysics
  • Cell Biology
  • Biochemistry

Background:

  • Cells interact with their environment via membrane-bound molecules.
  • Quantifying cell surface crowding and its impact on molecular interactions is challenging.

Purpose of the Study:

  • To develop a method for quantifying cell surface crowding.
  • To investigate how surface crowding affects macromolecular binding.
  • To explore the role of surface crowding in cell type and state.

Main Methods:

  • Combined experimental approaches with simulations.
  • Designed and utilized a novel crowding sensor.
  • Measured macromolecular binding (IgG antibodies) on reconstituted and live cell membranes.
  • Analyzed the contribution of specific molecules (sialic acid) to crowding.

Main Results:

  • Cell surface crowding attenuates macromolecular binding affinity in a dose-dependent manner.
  • Crowding decreased IgG antibody binding by 2- to 20-fold on live cells compared to bare membranes.
  • Sialic acid significantly contributes to red blood cell surface crowding.
  • Observed cell-type-specific differences in surface crowding.
  • Found that oncogene expression can alter surface crowding.

Conclusions:

  • Developed a quantitative sensor for cell surface crowding.
  • Demonstrated that surface crowding modulates biophysical interactions.
  • Surface crowding is a quantifiable characteristic that varies by cell type and state, potentially serving as a biomarker.