Accuracy of direct gradient sensing by cell-surface receptors

Area of Science:

• Biophysics
• Cell Biology
• Biochemistry

Background:

• Eukaryotic cells utilize cell-surface receptors to detect shallow chemical gradients, a crucial process for functions like chemotaxis.
• Accurate gradient sensing requires resolving small differences in diffusing particle arrival rates, complicated by random receptor binding and unbinding events.
• Previous models established physical limits of gradient sensing but lacked explicit particle-receptor kinetics.

Purpose of the Study:

• To quantify the accuracy of eukaryotic cell gradient sensing considering realistic particle-receptor kinetics.
• To investigate the impact of particle rebinding on the precision of chemotactic gradient detection.
• To derive analytical results for gradient sensing accuracy with different receptor configurations.

Main Methods:

• Utilized the fluctuation-dissipation theorem (FDT) to model receptor kinetics and noise.
• Developed a theoretical framework incorporating explicit particle-receptor binding and unbinding rates.
• Analyzed gradient sensing accuracy for models with two individual receptors and two coaxial rings of receptors.

Main Results:

• Particle rebinding to cell-surface receptors significantly lowers the accuracy of gradient sensing.
• Analytical results demonstrate reduced sensing precision due to receptor kinetics, consistent with prior findings.
• The study provides quantitative insights into the physical limitations imposed by receptor dynamics on chemotaxis.

Conclusions:

• Particle rebinding is a significant source of noise that impairs the accuracy of chemotactic gradient sensing.
• The fluctuation-dissipation theorem provides a powerful framework for analyzing the biophysics of cell surface receptor signaling.
• Understanding these kinetic limitations is essential for comprehending cellular responses to chemical cues.