Noise filtering tradeoffs in spatial gradient sensing and cell polarization response

Area of Science:

• Cell biology
• Biophysics
• Systems biology

Background:

• Cells sense chemical gradients for polarization, a process vital for functions like cell motility and division.
• Chemical gradient noise, caused by concentration fluctuations, can disrupt accurate cell polarization and spatial sensing.

Purpose of the Study:

• To investigate how external gradient noise impacts cellular spatial sensing and polarization.
• To identify and evaluate noise-filtering strategies and their associated tradeoffs in cell polarization.

Main Methods:

• Developed a coarse-grained mathematical model of gradient-sensing and cell polarity.
• Analyzed noise effects on a mechanistic model of yeast cell polarization.
• Conducted microfluidics experiments to test yeast cell orientation to shallow pheromone gradients.

Main Results:

• Noise negatively impacts polarization extent, accuracy, and output smoothness.
• A combination of positive feedback, multiple signaling stages, and time-averaging effectively filters noise.
• Yeast cells utilize a filter-amplifier architecture with dual positive feedback loops for noise tolerance, albeit with slower polarization.
• Yeast cells can detect shallow gradients (~0.1% μm-1), comparable to other motile eukaryotes.

Conclusions:

• Spatial noise significantly hinders cell polarization; effective filtering strategies are crucial.
• A filter-amplifier architecture with slow dynamics provides robust noise tolerance.
• Yeast cells employ complex filtering mechanisms for accurate gradient sensing, leading to a slow but precise polarization response.