Pancreatic Epithelial Cells Form Islet-Like Clusters in the Absence of Directed Migration

Associate Editor Michael R. King oversaw the review of this article. Abstract—The endocrine differentiation of pancreatic ductal epithelial cells is dependent upon their transition from a two-dimensional monolayer to three-dimensional islet-like clus-ters. Although clustering of these cells is commonly observed in vitro, it is not yet known whether clustering results from long-range signaling (e.g., chemotaxis) or short-range inter-actions (e.g., differential adhesion). To determine the mechanism behind clustering, we used experimental and computational modeling to determine the individual contri-butions of long-range and short-range interactions. Ex-perimentally, the migration of PANC-1 cells on tissue culture treated plastic was tracked by time-lapse microscopy with or without a central cluster of cells that could act as a concentrated source of some long-range signal. Cell migra