Using stochastic cell division and death to probe minimal units of cellular replication

Area of Science:

• Microbiology
• Cell Biology
• Biophysics

Background:

• The invariant cell initiation mass in bacteria suggests a minimal unit for cellular replication.
• This concept implies a potential coupling between stochastic cell division and death rates.

Purpose of the Study:

• To investigate the coupling between cell division and death rates in *Escherichia coli* under antibiotic stress.
• To explore the role of minimal replication units in driving these coupled rates.

Main Methods:

• Live and dead cell tracking in *Escherichia coli* populations treated with a ribosome-targeting antibiotic.
• Macroscopic growth/decay measurements and analysis of the growth exponent.
• Development and application of a stochastic model of cells as collections of 'widgets' (minimal replicating units).

Main Results:

• The growth exponent correlates with the difference between microscopic first-order cell division and death rates.
• The minimal inhibitory concentration (MIC) represents a dynamic equilibrium where division and death rates are high and balanced.
• A 'widget' model accurately reproduces experimental steady-state and transient dynamics, linking sub-cellular fluctuations to cell fate.

Conclusions:

• Cellular replication involves a dynamic interplay between division and death rates, governed by minimal units ('widgets').
• High division and death rates at MIC are driven by fluctuations in widget numbers.
• Further study of cells at the threshold of death could elucidate the molecular properties of these minimal replication units.