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Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling.
Kei Sugihara1, Koichi Nishiyama2, Shigetomo Fukuhara3
1Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Cell Reports
|December 15, 2015
Summary
This study introduces a mathematical model to understand how endothelial cells (ECs) move during blood vessel formation. The model reveals that cell-autonomous actions and coordinated cell behaviors drive angiogenesis, improving our understanding of multicellular dynamics.
Area of Science:
- Cell Biology
- Developmental Biology
- Biophysics
Background:
- Angiogenesis, the formation of new blood vessels, is a complex multicellular process driven by cell movements.
- Previous research highlighted dynamic and complex behaviors of vascular endothelial cells (ECs) during morphogenesis.
- The precise mechanisms governing individual EC movements in angiogenic morphogenesis are not fully understood.
Purpose of the Study:
- To systematically dissect the cellular mechanisms underlying EC movements in angiogenic branch elongation.
- To develop an experiment-driven mathematical model for analyzing multicellular behaviors in angiogenesis.
- To elucidate the interplay between cell-autonomous and coordinated actions in EC dynamics.
Main Methods:
- Development of an experiment-driven mathematical model to simulate EC behaviors.
- Systematic dissection of cellular mechanisms involved in branch elongation.
- Experimental verification and refinement of the mathematical model.
- Analysis of single-cell and cell-population dynamics.
Main Results:
- Cell-autonomous and coordinated actions were identified as key drivers of multicellular behaviors in angiogenesis.
- A cell-autonomous process was found to sufficiently explain essential features of morphogenetic EC dynamics.
- A coordinated mode of tip EC behavior, regulated by spatial relationships with follower ECs, was identified, enhancing tip cell motility.
- The model successfully illustrated essential features of morphogenetic EC dynamics at both single-cell and population levels.
Conclusions:
- The study provides a mechanistic understanding of endothelial cell behaviors during angiogenic morphogenesis.
- Findings highlight the importance of both cell-autonomous and coordinated cellular actions in multicellular development.
- The developed model offers insights into other multicellular phenomena beyond angiogenesis.
- The identified coordinated mode of tip EC behavior is crucial for efficient forward motility during vessel growth.
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