Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715012401 |
| _version_ | 1818849753340837888 |
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| author | Kei Sugihara Koichi Nishiyama Shigetomo Fukuhara Akiyoshi Uemura Satoshi Arima Ryo Kobayashi Alvaro Köhn-Luque Naoki Mochizuki Toshio Suda Hisao Ogawa Hiroki Kurihara |
| author_facet | Kei Sugihara Koichi Nishiyama Shigetomo Fukuhara Akiyoshi Uemura Satoshi Arima Ryo Kobayashi Alvaro Köhn-Luque Naoki Mochizuki Toshio Suda Hisao Ogawa Hiroki Kurihara |
| author_sort | Kei Sugihara |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T06:38:15Z |
| format | Article |
| id | doaj.art-5a23fa822fbf48e2a6ccc74b8e538978 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T06:38:15Z |
| publishDate | 2015-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5a23fa822fbf48e2a6ccc74b8e5389782022-12-21T20:32:10ZengElsevierCell Reports2211-12472015-12-011391814182710.1016/j.celrep.2015.10.051Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical ModelingKei Sugihara0Koichi Nishiyama1Shigetomo Fukuhara2Akiyoshi Uemura3Satoshi Arima4Ryo Kobayashi5Alvaro Köhn-Luque6Naoki Mochizuki7Toshio Suda8Hisao Ogawa9Hiroki Kurihara10Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Physiological Chemistry and Metabolism, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, JapanDepartment of Retinal Vascular Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Physiological Chemistry and Metabolism, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526, JapanDepartment for Innovative Methods of Computing, Center for Information Services and High Performance Computing (ZIH), Technische Universität Dresden, 01062 Dresden, GermanyDepartment of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, JapanInternational Research Center for Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, JapanDepartment of Physiological Chemistry and Metabolism, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanAngiogenesis 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.http://www.sciencedirect.com/science/article/pii/S2211124715012401 |
| spellingShingle | Kei Sugihara Koichi Nishiyama Shigetomo Fukuhara Akiyoshi Uemura Satoshi Arima Ryo Kobayashi Alvaro Köhn-Luque Naoki Mochizuki Toshio Suda Hisao Ogawa Hiroki Kurihara Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling Cell Reports |
| title | Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling |
| title_full | Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling |
| title_fullStr | Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling |
| title_full_unstemmed | Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling |
| title_short | Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling |
| title_sort | autonomy and non autonomy of angiogenic cell movements revealed by experiment driven mathematical modeling |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715012401 |
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