Big picture: Directional sensing can be a receptor-level computation driven by diffusion + degradation + feedback.
This explains puzzling experiments (e.g., why blocking endocytosis impairs chemotaxis) and suggests a general biophysical strategy across receptors families.
Predictions:
✔ There is an optimal diffusion rate for maximal polarization
✔ Receptors encode relative, not absolute, ligand gradients
✔ Cooperative receptor interactions can amplify weak gradients
All without requiring separate “local” and “global” signaling species.
The stochastic analysis is especially striking:
Noise reveals an optimal basal activity set point that maximizes signal-to-noise. Too little activity → noisy. Too much → less directional contrast. Biology tunes itself in between.
Add diffusion, and something remarkable happens:
Receptors move from low-ligand regions to high-ligand regions, but degradation depletes them where ligand is high.
This mismatch creates polarized receptor activity-directional sensing emerges naturally.
I will be talking about some recent work on using niche theory to model host associated microbiomes in a couple of hours!
Without diffusion, degradation implements integral feedback: receptor activity adapts perfectly to a ligand-independent set point-essential for sensing relative changes rather than absolute ligand levels.
The key ingredients:
• Receptor diffusion along the membrane
• Basal (ligand-independent) activity
• Selective degradation of active receptors
Together, these create an integral feedback loop (as opposed to an IFFL in LEGI) at the cell surface.
Classic models of eukaryotic directional sensing (e.g., LEGI) assume receptors are passive: they report ligand levels, while intracellular networks compare “local vs global” signals using incoherent feedforward loops. We asked: can receptors do the computation directly?