UC Santa Barbara

Active materials are a collection of self-driven units that independently operate to give a material unique, large-scale, global properties (e.g., flock of birds). Mammalian epithelia, which comprise our skin and provides a barrier layer for all our organs, is one of the best examples of active material. For example, when local regions of epithelial cells within a tissue are damaged, neighboring cells can rearrange via active migration to maintain the integrity of the tissue. As a material, the epithelium offers large potential in advancing synthetic biology for engineering active materials that can locally repair themselves when damaged, or globally alter their mechanical properties to adapt to a particular environment. The goal of my research is to understand how epithelial cells signal in response to mechanical cues, and how these changes influence their collective properties. This work will ultimately guide an approach to create synthetic materials with similar characteristics.

Recent work in our lab has demonstrated that mechanical forces on the epithelium, which occur regularly during development, also influence cell migration. These forces occur through tugging tensile forces between cells (e.g., neural tube development, gastrulation, lung epithelial stretch), sliding shear forces as cells slip past one another (e.g., gastrulation and fruit fly genitalia development), or some combination of the two. However, the molecular and biophysical mechanisms that result from epithelial cell-cell force transmission to drive collective migration are largely unknown. New experimental and computational models can help answer new questions regarding how epithelial cells transmit mechanical signals. These experiments require external and often custom micromanipulation methods.

This thesis attempts to better understand the relationship between epithelial cell-cell signaling and global epithelium behavior on multiple scales. Each study (i.e., chapter) becomes progressively more reduced, starting at the tissue level and ending at the single cell level. Methods within each study involve designing and developing novel experimental platforms that apply mechanical stresses to epithelial tissue. We utilize a programmable cell stretching platform, protein patterning, high-throughput cell segmentation, direct micromanipulation of cell-cell contacts, among other experimental and computational methods. This multi-hierarchical model introduces new tools to better elucidate cell-cell mechanosignaling across the protein and tissue level.