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Improving 2D and 3D Skin In Vitro Models Using Macromolecular Crowding
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(Macro)Molecular Crowding Effects Beyond Volume Exclusion.

Boris Y Zaslavsky1, Vladimir N Uversky2

  • 1Cleveland Diagnostics, Cleveland, OH, USA.

Sub-Cellular Biochemistry
|September 26, 2025
PubMed
Summary
This summary is machine-generated.

Macromolecular crowding significantly impacts protein behavior beyond simple excluded volume effects. This review explores additional factors like diffusion, viscosity, and solvent property changes in crowded biological environments.

Keywords:
Aqueous two-phase systemExcluded volume effectMacromolecular crowdingPartitionSoft interactionsSolvent propertiesViscosity

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Area of Science:

  • Biochemistry
  • Biophysics
  • Molecular Biology

Background:

  • Macromolecular crowding influences protein folding, binding, enzymatic activity, and aggregation.
  • The traditional view attributes crowding effects primarily to excluded volume interactions.
  • A deeper understanding requires considering additional factors beyond excluded volume.

Purpose of the Study:

  • To review and highlight key factors influencing protein behavior in crowded environments.
  • To expand the understanding of macromolecular crowding beyond excluded volume effects.
  • To emphasize the role of crowders on solvent properties and direct interactions.

Main Methods:

  • Literature review of studies on macromolecular crowding.
  • Analysis of factors affecting protein dynamics and interactions in crowded solutions.
  • Synthesis of current knowledge on non-excluded volume effects.

Main Results:

  • Crowded environments introduce perturbed diffusion and altered solution viscosity.
  • Soft interactions and direct physical contact between crowders and proteins are significant.
  • Crowders substantially modify solvent properties, impacting protein behavior.

Conclusions:

  • Protein behavior in crowded solutions is a complex interplay of multiple factors.
  • Excluded volume is insufficient to fully explain crowding effects on proteins.
  • Considering perturbed diffusion, viscosity, interactions, and solvent effects is crucial for a comprehensive understanding.