Characterization of Colliding Tissues: The Role of Geometry in Epithelial Gap Closure

Abstract

Until recently, much of the work in the wound healing subset of tissue engineering has aimed at optimizing in vitro assays and characterizing cell-cell interactions during expansion. This type of work is fundamental to understanding collective behavior in cell sheets and is a necessary step for future work, yet there has been a lack of research in this field regarding behavior after a monolayer has fully healed. It is critical to begin to fill this gap because initial closing of a wound is only half the battle, with scar formation and integrity being of upmost importance in later stages of self-healing. The work in this thesis is chiefly based around two parameters in a typical wound healing assay of MDCK cells. First, the influence on boundary formation after collision of two monolayers with varying geometries is observed and compared with predictive MATLAB modeling. It was found that when edges of monolayers having different curvature collide, a parabolic boundary will form rather than a straight boundary. Most of this behavior can be predicted through the model, except for some unforeseen density effects in more extreme cases. The second parameter explored in this project is concerned with competitive interactions at the tissue-tissue interface, which has been related to studies of invasive tumors near healthy tissue. By varying density in two colliding monolayers, it was found that boundary displacement could be forced rather quickly and in a manner similar to recent studies of Ras-transformed monolayers. Recreating this behavior shows that an otherwise healthy tissue can just as easily exert forces of a mutated tissue onto a nearly identical monolayer.