Biomaterial strategies to control cellular crowd behaviors

Abstract

Like bird flocks, fish schools, and human societies, cells need to coordinate their behaviors as a group to achieve desired biological functions, including collective migration, self-organization for cell fate patterning, and maintaining their homeostasis. There has been interest not only in understanding the mechanism of how tissue coordinates in concert but also in controlling their behaviors throughout the centuries. In this work, we introduce creative biomaterial approaches tomodulate the collective behaviors of epithelial and induced pluripotent stem cells. The initial segment of the thesis investigates the behavior of millimeter-scale epithelial tissue on a 'Janus substrate'—a surface coated with juxtaposed matrix and cell-cell junction proteins (cadherin). By altering the mechanism of cellular attachment from cell-matrix to cell-cell adhesion on the substrate, distinct migration dynamics, intercellular communication, and cellular division patterns emerge. These changes, resembling forced homeostatic conditions, are attributed to altered signaling pathway activation or deactivation induced by the absence of integrins on the cadherin substrate. The second focus of this study involves steering self-organization for stem cell differentiation using biomaterial approaches. Unlike current methods reliant on expensive micropatterning or complex microfluidic devices, we employ accessible bioengineering tools to pattern in vitro gastrulation and spatially activate signaling pathways. Utilizing a low-cost resin printer, we successfully replicate reported protein localization in 2D gastrulation differentiation following morphogen exposure. Additionally, we employ a transwell system to selectively expose morphogens from the basal compartment, leveraging the basolaterally polarized localization of morphogen receptors. In summary, this work presents toolkits for controlling larger-scale tissue collective dynamics and offers a more accessible approach to modulating stem cell differentiation. By bridging the gap between single-cell studies and future in vivo biomedical applications, these methodologies hold promise for advancing our understanding of cellular behavior and its implications in various biological contexts.