Direct Correlation between Motile Behavior and Protein Abundance in Single Cells

Area of Science:

• Microbiology
• Systems Biology
• Biophysics

Background:

• Stochastic molecular fluctuations significantly impact cellular behavior.
• Quantifying both behavior and protein levels within the same cell is crucial for understanding these effects.
• Non-genetic phenotypic diversity, such as in bacterial motility, influences single-cell exploration.

Purpose of the Study:

• To quantitatively map bacterial motility phenotype (tumble bias) to specific protein numbers.
• To investigate the impact of stochastic molecular fluctuations on bacterial behavior.
• To refine existing models of chemotaxis by incorporating key protein dynamics.

Main Methods:

• Combined automated microscopy with in situ hydrogel polymerization for simultaneous behavior tracking and protein expression measurement.
• Utilized fluorescently tagged chemotaxis proteins (CheR and CheB) expressed at varying levels.
• Performed thousands of single-cell measurements to analyze motility and protein abundance.

Main Results:

• Established a quantitative link between tumble bias and the cellular numbers of CheR and CheB proteins.
• Identified that CheB's role in receptor deamidation and slow receptor methylation fluctuations are critical for accurate modeling.
• Demonstrated that CheR and CheB levels independently modulate population mean tumble bias and its variance.

Conclusions:

• Adjusting global CheR and CheB expression levels can independently control population mean tumble bias and phenotypic diversity.
• Maintaining a constant CheR:CheB ratio ensures functional robustness.
• Non-genetic diversity in motility is likely selectable, conferring a potential selective advantage.