Increased accuracy of ligand sensing by receptor internalization

Area of Science:

• Cell biology
• Biophysics
• Biochemistry

Background:

• Cells utilize cell-surface receptors to detect external ligand concentrations with high precision.
• Receptor-mediated endocytosis (internalization) is a common cellular process with diverse functions.
• Internalization has been hypothesized to improve ligand sensing accuracy by preventing receptor overcounting.

Purpose of the Study:

• To investigate the impact of receptor internalization on the accuracy of cellular ligand concentration sensing.
• To develop a theoretical model explaining the relationship between internalization and sensing precision.

Main Methods:

• Extension of basic ligand-receptor models using principles of out-of-equilibrium thermodynamics.
• Mathematical modeling to quantify sensing accuracy in the presence and absence of internalization.
• Comparison of model predictions with experimental data from actual cellular receptors.

Main Results:

• The study demonstrates that receptor internalization significantly enhances the accuracy of external ligand concentration measurement.
• The developed thermodynamic model provides a quantitative explanation for this observed increase in sensing precision.
• Model predictions align with experimental rates of real-world receptors, confirming biological relevance.

Conclusions:

• Receptor internalization is a crucial mechanism for improving cellular sensitivity to external chemical signals.
• The findings offer a deeper understanding of the biophysical underpinnings of cellular sensing.
• This work bridges theoretical modeling with experimental observations in cell signaling.