Accuracy of direct gradient sensing by single cells.

Area of Science:

• Cellular Biology
• Biophysics
• Theoretical Biology

Background:

• Cells utilize chemotaxis to navigate chemical gradients, a process crucial for biological functions.
• Chemotaxis relies on cells inferring chemical gradients from diffusing particles interacting with surface receptors.
• While concentration sensing limits are known, physical limits for gradient sensing remain theoretically undefined.

Purpose of the Study:

• To derive a physical theory for the limits of gradient sensing in cells.
• To compare the efficacy of different cellular models for gradient inference.
• To provide a theoretical framework explaining observed cellular mechanisms in chemotaxis.

Main Methods:

• Developed a theoretical model using a perfectly absorbing sphere and a perfectly monitoring sphere as analogs for cell gradient sensing.
• Analyzed gradient inference based on absorbed surface particle density (absorbing sphere) and internal particle positions (monitoring sphere).
• Compared the theoretical predictions with experimental data from Dictyostelium discoideum (Dicty) navigating cAMP gradients.

Main Results:

• The perfectly absorbing sphere model demonstrated superior performance in both concentration and gradient sensing compared to the perfectly monitoring sphere.
• This superiority arises because absorbing models prevent re-measurement of previously encountered particles.
• The theory quantitatively aligns with experimental observations of Dicty's chemotactic behavior.

Conclusions:

• The physical limits of gradient sensing are theoretically defined by particle absorption and monitoring mechanisms.
• The absorbing sphere model provides a plausible explanation for signal-degrading enzymes (e.g., PDE, BAR1) found on cell surfaces.
• Cells, like Dicty, appear to operate close to the theoretical physical limits for gradient detection during chemotaxis.