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

Authored by Steven J Holfinger, James W Reinhardt, Rashmeet Reen, Kevin M Schultz, Kevin M Passino, William E Ackerman, Douglas A Kniss, Leonard M Sander, Daniel Gallego-Perez, Keith J Gooch

Date Published: 2015

DOI: 10.1007/s12195-015-0396-5

Sponsors: United States National Science Foundation (NSF)

Platforms: MATLAB

Model Documentation: Other Narrative

Model Code URLs: Model code not found

Abstract

The endocrine differentiation of pancreatic ductal epithelial cells is dependent upon their transition from a two-dimensional monolayer to three-dimensional islet-like clusters. 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 interactions (e.g., differential adhesion). To determine the mechanism behind clustering, we used experimental and computational modeling to determine the individual contributions of long-range and short-range interactions. Experimentally, 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 migration data was analyzed in terms of distance, number of steps, and migration rate in each direction, as well as migration rate as a function of distance from the cluster. Results did not indicate directed migration toward a central cluster (p > 0.05). Computationally, an agent-based model was used to demonstrate the plausibility of clustering by short-range interactions only. In the presence of random cell migration, this model showed that a high, but not maximal, cell-cell adhesion probability and minimal cell-substrate adhesion probability supported the greatest islet-like cluster formation.

Tags

differentiation chemotaxis Model Aggregation morphogenesis In-vitro Expression Precursor cells Insulin Transplantation