Physical limits of cells and proteomes

Area of Science:

• Cell biology
• Biophysics
• Protein dynamics

Background:

• Cellular physical limitations are often dictated by the proteome, comprising all cellular proteins.
• Understanding protein properties like size, stability, and folding/diffusion rates is crucial for cell physics.

Purpose of the Study:

• To formulate distributions and scaling relationships for cell physics using known protein data.
• To investigate the physical limits of cell behavior, including death temperature, growth rate, and internal density.

Main Methods:

• Combined known protein sizes, stabilities, and folding/diffusion rates.
• Utilized known protein-length distributions P(N) from Escherichia coli, yeast, and worm proteomes.
• Developed distributions and scaling relationships to model cell physics.

Main Results:

• Cell death temperature correlates with a proteome-wide denaturation catastrophe.
• High protein density (approx. 20% by volume) optimizes biochemical reaction rates by balancing protein collision frequency and diffusion speed.
• Cell growth is constrained by protein synthesis rates, slowest protein folding rates, and protein diffusion rates in larger cells.

Conclusions:

• Proteome denaturation cooperativity allows cell function close to death temperatures.
• Cellular density is optimized for maximal biochemical reaction rates.
• Scaling laws derived from protein knowledge bases offer insights into cell physics and limitations.