Linking tissue morphology and tissue healing in a cell-fate model

Area of Science:

• Developmental Biology
• Computational Biology
• Tissue Engineering

Background:

• Multicellular tissues exhibit diverse morphologies but share common microanatomical organization into domains.
• Tissue healing is a fundamental property across species, even those with limited regenerative capabilities.
• Both tissue organization and healing are products of developmental processes, suggesting an intrinsic link.

Purpose of the Study:

• To investigate the relationship between tissue morphology and healing capacity using a computational model.
• To explore how developmental cell-fate decisions influence tissue structure and function.
• To identify general principles of tissue organization and repair across different life forms.

Main Methods:

• Development of an agent-based model simulating cell-fate decisions during tissue development.
• Tuning four key parameters controlling cell interactions and differentiation to generate diverse tissue morphologies.
• Analysis of simulated tissue structures to assess their ability to heal from induced injuries.

Main Results:

• The model generated a spectrum of tissue structures, from sparse to densely organized domains, by varying interaction and differentiation parameters.
• Only simulated tissues with large, contiguous domains demonstrated the capacity for healing.
• Healing primarily occurred through the proliferation of neighboring cells, a mechanism observed in both plants and animals.

Conclusions:

• Tissue healing is strongly coupled to its macroscopic, domain-level morphology.
• The model demonstrates that organized tissue domains are crucial for effective repair.
• The findings suggest a unifying principle of multicellular life, linking tissue organization and healing capacity across diverse organisms.