Computational modeling of cellular-scale mechanics
During many biological processes, cells move through their surrounding environment by exerting mechanical forces. The mechanical forces are mainly generated by molecular interactions between actin filaments (F-actins) and myosin motors within the actin cytoskeleton. Forces are transmitted to the surrounding extracellular matrix via adhesions. In this thesis, we employed agent-based computational models to study the interactions between F-actins and myosin in the motility assay and the cell migration process. In the first project, the myosin motility assay was employed to study the collective behaviors of F-actins. Unlike most of the previous computational models, we explicitly represent myosin motors. By running simulations under various conditions, we showed how the length, bending stiffness, and concentration affect the collective behavior of F-actins. We found that four distinct structures formed: homogeneous networks, flocks, bands, and rings. In addition, we showed that mobile motors lead to the formation of distinct F-actin clusters that were not observed with immobile motors. In the second project, we developed a 3D migration model to define how cells mechanically interact with their 3D environment during migration. Unlike cells migrating on a surface, cells within 3D extracellular matrix (ECM) must remodel the ECM and/or squeeze their body through the ECM, which causes 3D cell migration to be significantly more challenging than 2D migration. Our model describes realistic structural and rheological properties of ECM, cell protrusion, and focal adhesions between cells and the ECM.
History
Degree Type
- Master of Science
Department
- Biomedical Engineering
Campus location
- West Lafayette