SEM²: Introducing mechanics in cell and tissue modeling using coarse-grained homogeneous particle dynamics

Area of Science:

• Biomedical Engineering
• Computational Biology
• Mechanobiology

Background:

• Modeling multiscale mechanics in engineered tissues is challenging due to complex cell behaviors.
• Subcellular Element Modeling (SEM) captures cell rheology but lacks explicit multiscale mechanics.
• Bridging cell-level dynamics and tissue-level deformations is crucial for understanding engineered tissues.

Purpose of the Study:

• Introduce a novel computational framework, Subcellular Element Modeling and Mechanics (SEM²), for multiscale tissue modeling.
• Incorporate particle-level stress and strain analysis into SEM to address limitations in existing models.
• Demonstrate the utility of SEM² in simulating cell behaviors and mechanical properties in engineered tissues.

Main Methods:

• Developed SEM² by integrating stress and strain analysis into the open-source SEM++ software.
• Applied SEM² to simulate single-cell creep, migration, and proliferation.
• Introduced a novel force to control nuclear positioning during cell migration and proliferation.

Main Results:

• SEM² successfully models emergent cell behaviors and provides insights into stress/strain distributions.
• Demonstrated the framework's capability to simulate proliferation in organoids and organs-on-chip.
• Validated SEM² through first-principles literature values and parametric studies.

Conclusions:

• SEM² provides a robust framework for analyzing multiscale mechanics in engineered tissues.
• The developed model enhances the simulation of cell behaviors like migration and proliferation.
• SEM² offers valuable tools for designing and understanding organoids and organs-on-chip.