Multiscale modelling shows how cell-ECM interactions impact ECM fibre alignment and cell detachment

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• The extracellular matrix (ECM) is crucial for cell behavior, growth, and migration.
• Cell-ECM interactions, particularly through focal adhesions, allow cells to sense matrix mechanics and exert forces.
• The mechanical interplay between cells and the ECM is complex and influenced by multiple factors across different scales.

Purpose of the Study:

• To develop a multiscale model integrating cell-ECM mechanical interactions.
• To quantify cell-cell communication mediated by ECM deformation.
• To investigate the influence of mechanical properties and network topology on cell-ECM interactions.

Main Methods:

• Developed a multiscale agent-based model.
• Integrated mechanosensitive focal adhesion regulation, cytoskeleton dynamics, and ECM deformation.
• Simulated mechanical force transmission and cell-ECM interplay.

Main Results:

• Cell-cell communication via ECM deformation depends on cell and ECM mechanical properties and network topology.
• Increased cell contraction leads to greater ECM deformation.
• A specific ECM stiffness optimizes mechanical cue transmission, while network topology impacts deformation transmission and can cause cell detachment.

Conclusions:

• Multiscale modeling is essential for understanding mechanical communication in cell-ECM interactions.
• ECM stiffness, cell contraction, and network topology are key regulators of mechanical signaling.
• The study provides insights into how physical forces shape cell behavior within the ECM.