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Updated: May 7, 2026

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates
Published on: January 5, 2024
DNA-binding-protein inhomogeneity in E. coli modeled as biphasic facilitated diffusion
Thomas E Kuhlman1, Edward C Cox
1Department of Physics, Center for the Physics of Living Cells, and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801-3080, USA.
Nonspecifically bound lac repressors show spatial inhomogeneity in E. coli cells. This is modeled as diffusion between DNA and cytoplasm, impacting target search.
Area of Science:
- Molecular Systems Biology
- Microbiology
- Biophysics
Background:
- Nonspecifically bound lac repressors exhibit spatial inhomogeneity within E. coli.
- This distribution is influenced by the encoding gene's location and DNA compaction.
Purpose of the Study:
- To model the spatial inhomogeneity of lac repressors in E. coli.
- To understand the role of intracellular diffusion and compartmentalization in protein distribution.
- To explore the implications for DNA-binding protein target search efficiency.
Main Methods:
- Computational modeling of intracellular diffusion.
- Phase separation model considering condensed DNA and cytoplasm.
- Analysis of lac repressor behavior within these compartments.
Main Results:
- Lac repressor inhomogeneity arises from diffusion and exchange between DNA and cytoplasmic phases.
- The model explains observed spatial distributions based on biophysical principles.
- Compartmentalization significantly affects the accessibility and search dynamics of lac repressors.
Conclusions:
- Intracellular compartmentalization and diffusion are key determinants of lac repressor localization.
- The proposed two-phase model provides a framework for understanding non-specific protein binding and target search in bacteria.
- This work has implications for gene regulation and the dynamics of DNA-protein interactions within living cells.
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