Avoiding tensional equilibrium in cells migrating on a matrix with cell-scale stiffness-heterogeneity

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Cell migration is crucial for development and disease.
• Cellular behavior is influenced by the extracellular matrix (ECM) stiffness.
• Intracellular stresses dynamically regulate cell functions during migration.

Purpose of the Study:

• To investigate intracellular stress dynamics (ISD) in cells migrating on heterogeneous ECM stiffness.
• To understand how spatial constraints and competing cellular taxis affect ISD.
• To explore the relationship between cell shape, migration, and stress response on microelastically patterned substrates.

Main Methods:

• Finite element method-based traction force microscopy (FEM-TFM) was employed.
• Cells were cultured on microelastically patterned gels with stiff/soft stripes and stiff triangular patterns.
• FEM-TFM quantified traction forces and stress dynamics during cell migration.

Main Results:

• Prolonged fluctuation of whole-cell scale traction stress was significantly enhanced on single cell-size triangular stiff patterns compared to homogeneous gels.
• Enhanced ISD resulted from the interplay between cell migration across stiffness gradients and domain shape-dependent traction force dynamics.
• Cellular taxis, including durotaxis and reverse durotaxis, influenced stress patterns.

Conclusions:

• Heterogeneous ECM stiffness, particularly with specific geometric patterns, can lead to enhanced intracellular stress fluctuations.
• The observed ISD is critical for maintaining cells away from tensional equilibrium.
• Understanding ISD in heterogeneous environments is essential for comprehending cell migration and tissue dynamics.