Cell Invasion Dynamics into a Three Dimensional Extracellular Matrix Fibre Network.

Area of Science:

• Biophysics
• Computational Biology
• Cell Biology

Background:

• Cell-extracellular matrix (ECM) interactions are crucial for cell functions.
• The mechanisms of filopodia interaction with 3D ECM are not well understood.

Purpose of the Study:

• To develop a computational model predicting filopodia dynamics within a 3D ECM.
• To investigate how filopodia interact with ECM fibers and influence cell migration.

Main Methods:

• Constructed an individual-based, force-based computational model integrating filopodia penetration, intracellular mechanics, ECM structural mechanics, and biochemical reaction-diffusion.
• Modeled filopodia-ECM interaction as a stochastic process based on binding kinetics.
• Integrated the filopodia model into whole-cell migratory dynamics.

Main Results:

• The model predicts filopodia tip movement along ECM fibers, tugging, contraction, or retraction based on binding strength, ECM stiffness, and pore size.
• Filopodia-ECM interactions are stochastic, influenced by integrin-ligand binding kinetics.
• Predicted average filopodia and cell membrane advance speeds closely matched experimental data for 3D HUVEC migration (r(2) > 0.95).

Conclusions:

• The developed computational model accurately captures filopodia dynamics and cell invasion in 3D ECM.
• The model provides insights into how physical and biochemical cues in the ECM regulate cell migration.
• This work enhances understanding of cell-ECM interactions in complex 3D environments.