Physical Limit to Concentration Sensing Amid Spurious Ligands

Area of Science:

• Cellular biology
• Biophysics
• Biochemical signaling

Background:

• Cells adapt to environmental changes by sensing external ligand concentrations via receptor binding.
• Nonspecific binding of incorrect ligands can interfere with accurate concentration sensing, especially at high concentrations.

Purpose of the Study:

• To analytically derive the physical limit of concentration sensing accuracy in the presence of interfering ligands.
• To identify the conditions and mechanisms that govern the precision of cellular sensing.

Main Methods:

• Analytical derivation of physical limits for concentration sensing.
• Analysis of ligand-receptor binding dynamics and nonspecific interference.
• Investigation of scaling transitions based on ligand binding times.

Main Results:

• A scaling transition in sensing accuracy is identified when the mean bound time of correct ligands is twice that of incorrect ligands.
• This transition defines a fundamental physical limit to cellular concentration sensing.
• The study provides a quantitative understanding of interference effects in biological sensing.

Conclusions:

• The physical limit of concentration sensing is analytically determined, providing a benchmark for cellular performance.
• Kinetic proofreading schemes, generalized through receptor states, can approach this physical bound.
• Understanding these limits is crucial for comprehending cellular adaptation and signaling fidelity.