An excitable cortex and memory model successfully predicts new pseudopod dynamics.

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Motile eukaryotic cells display directional persistence, often characterized by alternating left and right turns.
• The specific mechanisms driving this zig-zag movement, such as pseudopod extension patterns in Dictyostelium discoideum, are not fully understood.

Purpose of the Study:

• To propose and validate a novel computational model, the Excitable Cortex and Memory (EC&M) model, explaining the alternating pseudopod extension in eukaryotic cell migration.
• To investigate the role of cortical excitability and memory in directional cell persistence.

Main Methods:

• Developed the EC&M model, integrating concepts of excitable systems and global inhibition with a new hypothesis of localized cortical excitability as memory.
• Created an algorithm for pseudopod detection using hierarchical clustering of membrane extensions.
• Conducted cell-tracking experiments to validate model predictions.

Main Results:

• The EC&M model successfully reproduces the experimentally observed zig-zag behavior of cell migration.
• The model's four novel predictions regarding pseudopod dynamics were experimentally validated.
• Cell-tracking data confirmed that pseudopod placement is a non-Markovian process influenced by prior pseudopod activity.

Conclusions:

• The EC&M model provides a mechanistic explanation for zig-zag cell motility and directional persistence.
• The findings suggest that cell migration involves a memory-dependent process, challenging purely Markovian assumptions.
• This work offers a framework for future research into the molecular underpinnings of cell movement and directional persistence.