Dynamics of Cell Ensembles on Adhesive Micropatterns: Bridging the Gap between Single Cell Spreading and Collective Cell Migration
Philipp J. Albert, Ulrich S. Schwarz
Abstract
The collective dynamics of multicellular systems arise from the interplay of a few fundamental elements: growth, division and apoptosis of single cells; their mechanical and adhesive interactions with neighboring cells and the extracellular matrix; and the tendency of polarized cells to move. Micropatterned substrates are increasingly used to dissect the relative roles of these fundamental processes and to control the resulting dynamics. Here we show that a unifying computational framework based on the cellular Potts model can describe the experimentally observed cell dynamics over all relevant length scales. For single cells, the model correctly predicts the statistical distribution of the orientation of the cell division axis as well as the final organisation of the two daughters on a large range of micropatterns, including those situations in which a stable configuration is not achieved and rotation ensues. Large ensembles migrating in heterogeneous environments form non-adhesive regions of inward-curved arcs like in epithelial bridge formation. Collective migration leads to swirl formation with variations in cell area as observed experimentally. In each case, we also use our model to predict cell dynamics on patterns that have not been studied before.
Author Summary
The collective dynamics of many cells is more than the sum of its parts. For example, large cell collectives often form streams, swirls or bridges that cannot be achieved by single cells. Yet the dynamic processes of single cells, especially their response to adhesive and mechanical cues, stays an essential element of the collective cell dynamics. Here we introduce a comprehensive modeling framework that allows us to predict cellular dynamics from the level of single cells up to the level of large cell collectives on the same footing. We focus on cellular dynamics on adhesive micropatterns as an especially successful approach to investigate and control complex cell behaviour. Our model successfully predicts a large range of experimentally observed phenomena, allows us to investigate the relative importance of the different cellular processes and in the future can be used to design new adhesive micropatterns that promote desired cell dynamics.
Citation: Albert PJ, Schwarz US (2016) Dynamics of Cell Ensembles on Adhesive Micropatterns: Bridging the Gap between Single Cell Spreading and Collective Cell Migration. PLoS Comput Biol 12(4): e1004863. doi:10.1371/journal.pcbi.1004863
Editor: Feilim Mac Gabhann, Johns Hopkins University, UNITED STATES
Received: August 31, 2015; Accepted: March 11, 2016; Published: April 7, 2016
Copyright: © 2016 Albert, Schwarz. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: This work was supported by the European Union’s Seventh Framework Programme through the MEHTRICS-project (Micropattern Enhanced High Throughput RNA Interference for Cell Screening, http://www.mehtrics.com, grant agreement 278758). We also acknowledge support by the EcTop B programme (cytoskeleton) of the cluster of excellence CellNetworks. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
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