Computational Investigation of the Role of Mechanical Interactions on the Collective Cell Migration Behavior

Cell migration plays an essential role in many biological and physiological processes including morphogenesis, wound healing, and tumor metastases. Any abnormal migrations may result in severe defects or life-threatening scenarios, such as immunosuppression, autoimmune diseases, defective wound repair, or tumor formation and metastasis. To investigate the mechanisms underlying cell migration could lead to novel strategies and applications for controlling invasive tumor cells. Wound healing remains a challenging clinical problem and impaired wound healing affects 3~6 million people in the US. Epithelial wound healing is a complex process in which not only biochemical factors, but also physical factors play significant roles. Currently there are no advanced physics-based continuum models at cellular level which can capture the cell material property and deformation, cell-cell, cell-substrate interaction, etc. Therefore in this dissertation, our goal is to develop such continuum models to investigate the cell migration behavior. First (Essay Ⅰ), a continuum physics-based cell model was proposed using RKPM meshfree method to investigate the monocyte motility and intercellular adhesion during collective cell migration. Next (Essay Ⅱ), a two-dimensional finite element model was developed to study the cell migration behavior in a confluent epithelial monolayer, incorporating the interfacial interaction at each cell junction. Finally (Essay Ⅲ), a three-dimensional continuum computational model with finite element method was presented to investigate the mechanical factors that influence the wound healing process without cell division. Overall, the computational model developed in this study can be employed as a tool to unravel the mechanical principles behind the complex collective cell migration process. Results of this study might have the potential to improve effective medical management and optimize the treatment.