Journal article
Propagating Waves of Directionality and Coordination Orchestrate Collective Cell Migration
PLoS Computational Biology, Vol.10(7), e1003747
Jul/2014
Abstract
The ability of cells to coordinately migrate in groups is crucial to enable them to travel long distances during embryonic development, wound healing and tumorigenesis, but the fundamental mechanisms underlying intercellular coordination during collective cell migration remain elusive despite considerable research efforts. A novel analytical framework is introduced here to explicitly detect and quantify cell clusters that move coordinately in a monolayer. The analysis combines and associates vast amount of spatiotemporal data across multiple experiments into transparent quantitative measures to report the emergence of new modes of organized behavior during collective migration of tumor and epithelial cells in wound healing assays. First, we discovered the emergence of a wave of coordinated migration propagating backward from the wound front, which reflects formation of clusters of coordinately migrating cells that are generated further away from the wound edge and disintegrate close to the advancing front. This wave emerges in both normal and tumor cells, and is amplified by Met activation with hepatocyte growth factor/scatter factor. Second, Met activation was found to induce coinciding waves of cellular acceleration and stretching, which in turn trigger the emergence of a backward propagating wave of directional migration with about an hour phase lag. Assessments of the relations between the waves revealed that amplified coordinated migration is associated with the emergence of directional migration. Taken together, our data and simplified modeling-based assessments suggest that increased velocity leads to enhanced coordination: higher motility arises due to acceleration and stretching that seems to increase directionality by temporarily diminishing the velocity components orthogonal to the direction defined by the monolayer geometry. Spatial and temporal accumulation of directionality thus defines coordination. The findings offer new insight and suggest a basi
Details
- Title
- Propagating Waves of Directionality and Coordination Orchestrate Collective Cell Migration
- Creators
- Assaf Zaritsky (null)Doron Kaplan (null)Inbal Hecht (null)Sari Natan (null)Lior Wolf (null)Nir Gov (null) - 972WIS_INST___136Eshel Ben-Jacob (null)Ilan Tsarfaty (null)
- Resource Type
- Journal article
- Publication Details
- PLoS Computational Biology, Vol.10(7), e1003747; Jul/2014
- Number of pages
- 15
- Language
- English
- DOI
- https://doi.org/10.1371/journal.pcbi.1003747
- Grant note
- Breast Cancer Research Foundation; Federico Foundation Grants; US - Israel Binational Science Foundation; Tauber Family Foundation at Tel Aviv University; Center for Theoretical Biological Physics - NSF [PHY-0822283]; Cancer Prevention and Research Institute of Texas (CPRIT) at Rice UniversityThe work was supported in part by grants from the Breast Cancer Research Foundation; the Federico Foundation Grants; the US - Israel Binational Science Foundation and the Tauber Family Foundation at Tel Aviv University, the Center for Theoretical Biological Physics sponsored by the NSF (# PHY-0822283), and by the Cancer Prevention and Research Institute of Texas (CPRIT) at Rice University. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript._ALMAME_DELIMITER_
- Record Identifier
- 993263991403596
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