Reconstructing Actin Dynamics of the Leading Edge from Observational Data

Area of Science:

• Cell Biology
• Biophysics
• Systems Biology

Background:

• Mesenchymal cell migration relies on leading-edge protrusion, driven by actin network dynamics.
• Traditional models of cell protrusion use perturbative experiments, limiting understanding of natural cellular processes.
• Recent advances in multiplex microscopy provide non-perturbative data on protein fluctuations at the cell leading edge.

Purpose of the Study:

• To reconstruct a mechanistic model of cell protrusion dynamics from non-perturbative microscopy data.
• To analyze the coupled dynamics of F-actin, Arp2/3 protein complex, and cell edge velocity.
• To develop a nonlinear partial differential equation model for lamellipodial dynamics.

Main Methods:

• Analysis of F-actin and Arp2/3 density fluctuations and cell edge velocity using phase space and regression.
• Reconstruction of linearized stochastic actin-Arp2/3-velocity coupled dynamics.
• Development of a nonlinear partial differential equation model based on experimental data and prior knowledge.

Main Results:

• The model successfully recovers reaction rates and transport processes in the lamellipodium.
• Identified retrograde flow of F-actin as the primary source of nonlinearity.
• Revealed that protrusion is governed by a damped oscillatory cycle due to feedback mechanisms.

Conclusions:

• A novel, non-perturbative method for modeling cell protrusion dynamics has been established.
• The model elucidates the interplay between actin, Arp2/3, and cell velocity in driving cell migration.
• The findings highlight the significance of feedback loops in regulating lamellipodial}$.
• The findings highlight the significance of feedback loops in regulating lamellipodial dynamics and cell protrusion.