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Single Molecule Fluorescence Energy Transfer Study of Ribosome Protein Synthesis
Published on: July 6, 2021
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Colloidal Physics Modeling Reveals How Per-Ribosome Productivity Increases with Growth Rate in Escherichia coli
Akshay J Maheshwari1, Alp M Sunol2, Emma Gonzalez2
1Department of Bioengineering, Stanford University, Stanford, California, USA.
Mbio
|December 20, 2022
Summary
Faster cell growth requires more productive ribosomes. A new physics model shows that molecular proximity, not faster diffusion, explains increased ribosome productivity in crowded cells, potentially limiting growth rates.
Area of Science:
- Cellular Biology
- Biophysics
- Systems Biology
Background:
- Faster cell growth necessitates increased protein synthesis.
- Increased ribosome abundance partially explains higher protein synthesis rates.
- Individual ribosome productivity must also increase, but the mechanism remains unclear.
Purpose of the Study:
- To investigate the mechanism behind increased individual ribosome productivity during faster cell growth.
- To explore the interplay of physical crowding, molecular transport, and stoichiometry in cellular processes.
- To develop a physics-based model of *Escherichia coli* cytoplasm.
Main Methods:
- Constructed a first-principles, physics-based computational model of *Escherichia coli* cytoplasm.
- Modeled Brownian motion and diffusion based on molecular interactions, size, density, and abundance.
- Analyzed the contribution of physical transport to translation elongation latency.
Main Results:
- Predicted that physical transport of ternary complexes accounts for approximately 80% of translation elongation latency.
- Observed that volumetric crowding increases with faster growth, while cytoplasmic mass density remains constant.
- Demonstrated that improved proximity between ternary complexes and ribosomes overcomes slowed diffusion, enhancing ribosome productivity.
Conclusions:
- Physical crowding, transport, and stoichiometry provide a mechanism for increased individual ribosome productivity.
- Cellular crowding may impose a physical limitation on cell growth rates.
- Colloidal-scale modeling offers a "physics engine" for systems biology to study molecular-level transport and reactions.
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