A diffusion-translocation model for gradient sensing by chemotactic cells

Area of Science:

• Cell Biology
• Biophysics
• Biochemistry

Background:

• Chemotactic cells, such as Dictyostelium and neutrophils, can amplify shallow chemoattractant gradients into localized intracellular signals.
• Understanding the biophysical mechanisms behind this signal localization is key to comprehending cellular responses.

Purpose of the Study:

• To investigate the biophysical parameters governing the establishment and maintenance of localized second messenger signals within cells.
• To explore how positive feedback mechanisms and component translocation contribute to signal amplification and localization.
• To model the process of gradient sensing and signal transduction in chemotactic cells.

Main Methods:

• Mathematical modeling of second messenger dynamics, considering dispersion range (lambda) and degradation rate (k(-1)).
• Analysis of models incorporating cytosolic component translocation to the plasma membrane.
• Simulation of signal transduction cascades with varying numbers of translocating components.

Main Results:

• The dispersion range (lambda) of second messengers, determined by diffusion (D(m)) and degradation (k(-1)), must be small relative to cell length for effective localization.
• Short-lived second messengers (high k(-1)) with diffusion coefficients between 0-5 microm(2) s(-1) are optimal for signal localization.
• Models with translocating components demonstrate significant nonlinear amplification, converting shallow receptor activity differences into large second messenger concentration gradients.
• Cytosolic component depletion mediates communication between cell regions, leading to local activation and global inhibition.

Conclusions:

• Signal localization in chemotactic cells relies on second messengers with restricted dispersion ranges and short lifetimes.
• Translocation of signaling components and positive feedback mechanisms are crucial for amplifying shallow gradients.
• The proposed biochemical mechanism provides a general explanation for signal localization phenomena in cell signaling, morphogenesis, and differentiation.