Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling

Kei Sugihara, Koichi Nishiyama, Shigetomo Fukuhara, Akiyoshi Uemura, Satoshi Arima, Ryo Kobayashi, Alvaro Köhn-Luque, Naoki Mochizuki, Toshio Suda, Hisao Ogawa, Hiroki Kurihara

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Angiogenesis is a multicellular phenomenon driven by morphogenetic cell movements. We recently reported morphogenetic vascular endothelial cell (EC) behaviors to be dynamic and complex. However, the principal mechanisms orchestrating individual EC movements in angiogenic morphogenesis remain largely unknown. Here we present an experiment-driven mathematical model that enables us to systematically dissect cellular mechanisms in branch elongation. We found that cell-autonomous and coordinated actions governed these multicellular behaviors, and a cell-autonomous process sufficiently illustrated essential features of the morphogenetic EC dynamics at both the single-cell and cell-population levels. Through refining our model and experimental verification, we further identified a coordinated mode of tip EC behaviors regulated via a spatial relationship between tip and follower ECs, which facilitates the forward motility of tip ECs. These findings provide insights that enhance our mechanistic understanding of not only angiogenic morphogenesis, but also other types of multicellular phenomenon.

Original languageEnglish
Pages (from-to)1814-1827
Number of pages14
JournalCell Reports
Issue number9
Publication statusPublished - Dec 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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