Computational design for engineering layered tissue architectures via cellular interfacial tension modulation

Area of Science:

• Biophysics
• Tissue Engineering
• Computational Biology

Background:

• The spatial arrangement of cells is crucial for three-dimensional (3D) tissue integrity.
• Engineering precisely controlled tissue architectures is a significant challenge in regenerative medicine.

Purpose of the Study:

• To computationally investigate the design of layered tissue architectures by modulating tension at cellular interfaces.
• To identify interfacial tension as a tunable parameter for regulating tissue structure.

Main Methods:

• Utilized a 3D vertex model for computational simulations.
• Systematically varied interfacial tension magnitudes at free-surface and cell-cell interfaces.
• Analyzed resulting tissue architectures in both homogeneous and heterogeneous cell populations.

Main Results:

• Increasing interfacial tension promoted transitions from monolayers to structurally stratified tissues in homogeneous populations.
• Differential interfacial tensions induced cell sorting and multilayer formation in heterogeneous populations.
• A recursive tension strategy enabled hierarchical organization of multiple cell types into distinct layers.

Conclusions:

• Cell-cell interfacial tension is a key mechanical regulator for designing layered tissue architectures.
• These findings provide foundational design principles for advancing tissue engineering and regenerative medicine.
• The recursive tension strategy offers a scalable method for creating complex, multi-layered tissue constructs.