Development of a three dimensional multiscale computational model of the human epidermis

Area of Science:

• Computational biology
• Dermatology
• Tissue regeneration

Background:

• Transforming Growth Factor-beta1 (TGF-beta1) is vital for tissue regeneration but paradoxically inhibits keratinocyte proliferation during re-epithelialization.
• Existing biological models offer limited comprehensive understanding of TGF-beta1's regulatory functions.
• A computational approach is needed to complement experimental studies and elucidate TGF-beta1's complex actions.

Purpose of the Study:

• To develop a comprehensive, three-dimensional, multiscale computational model of the human epidermis.
• To integrate cellular, subcellular, and multicellular levels of biological organization to simulate TGF-beta1 signaling and keratinocyte behavior.
• To provide a novel tool for investigating the functions of TGF-beta1 in epidermal wound healing.

Main Methods:

• Developed a 3D multiscale model integrating an agent-based model for cellular rules, a COmplex PAthway SImulator (COPASI) for TGF-beta1 signaling, and a mechanical layer for cell-cell forces.
• Validated the model by simulating virtual epidermis growth and comparing simulation results with existing literature on keratinocyte behavior and TGF-beta1 signaling.
• The model captures emergent behaviors following injury and interactions between different epidermal layers.

Main Results:

• The integrated model successfully simulated virtual epidermis formation in 3D.
• Simulations of keratinocyte behavior and TGF-beta1 signaling aligned with established research findings.
• The model provides a robust platform for exploring complex biological processes computationally.

Conclusions:

• Computational modeling offers an effective complementary approach to experimental methods for understanding complex biological systems like epidermal wound healing.
• The developed 3D multiscale model serves as a valuable tool for investigating TGF-beta1's role at cellular and subcellular levels.
• Further research using this model can elucidate specific hypotheses regarding TGF-beta1 functions in different keratinocyte populations during healing.