Coordinated linear and rotational movements of endothelial cells compartmentalized by VE-cadherin drive angiogenic sprouting

Kazuo Tonami; Tatsuya Hayashi; Yasunobu Uchijima; Masahiro Kanai; Fumitaka Yura; Jun Mada; Kei Sugahara; Yukiko Kurihara; Yuri Kominami; Toshiyuki Ushijima; Naoko Takubo; Xiaoxiao Liu; Hideto Tozawa; Yoshimitsu Kanai; Tetsuji Tokihiro; Hiroki Kurihara

doi:10.1016/j.isci.2023.107051

Coordinated linear and rotational movements of endothelial cells compartmentalized by VE-cadherin drive angiogenic sprouting

iScience. 2023 Jun 7;26(7):107051. doi: 10.1016/j.isci.2023.107051. eCollection 2023 Jul 21.

Authors

Kazuo Tonami^{1

2}, Tatsuya Hayashi^{2

3

4}, Yasunobu Uchijima¹, Masahiro Kanai⁵, Fumitaka Yura⁶, Jun Mada⁷, Kei Sugahara¹, Yukiko Kurihara¹, Yuri Kominami⁸, Toshiyuki Ushijima¹, Naoko Takubo^{1

2

9}, Xiaoxiao Liu¹, Hideto Tozawa¹⁰, Yoshimitsu Kanai¹¹, Tetsuji Tokihiro^{2

3

12}, Hiroki Kurihara^{1

2}

Affiliations

¹ Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan.
³ Graduate School of Mathematical Science, The University of Tokyo, 3-8-1, Komaba, Meguro-ku, Tokyo 153-8914, Japan.
⁴ Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
⁵ Department of Education and Creation Engineering, Kurume Institute of Technology, 2228-66 Kamitsu-machi, Kurume, Fukuoka 830-0052, Japan.
⁶ Department of Complex and Intelligent Systems, School of Systems Information Science, Future University Hakodate, 116-2 Kamedanakano-cho, Hakodate, Hokkaido 041-8655, Japan.
⁷ College of Industrial Technology, Nihon University, 2-11-1 Shin-ei, Narashino, Chiba 275-8576, Japan.
⁸ Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-865, Japan.
⁹ Isotope Science Center, The University of Tokyo, 2-11-16, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
¹⁰ Department of Chemistry, Graduate School of Science, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
¹¹ Cell Biology and Anatomy, Graduate School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
¹² Department of Mathematical Engineering, Faculty of Engineering, Musashino University, 3-3-3 Ariake, Koto-ku, Tokyo 135-8181, Japan.

Abstract

Angiogenesis is a sequential process to extend new blood vessels from preexisting ones by sprouting and branching. During angiogenesis, endothelial cells (ECs) exhibit inhomogeneous multicellular behaviors referred to as "cell mixing," in which ECs repetitively exchange their relative positions, but the underlying mechanism remains elusive. Here we identified the coordinated linear and rotational movements potentiated by cell-cell contact as drivers of sprouting angiogenesis using in vitro and in silico approaches. VE-cadherin confers the coordinated linear motility that facilitated forward sprout elongation, although it is dispensable for rotational movement, which was synchronous without VE-cadherin. Mathematical modeling recapitulated the EC motility in the two-cell state and angiogenic morphogenesis with the effects of VE-cadherin-knockout. Finally, we found that VE-cadherin-dependent EC compartmentalization potentiated branch elongations, and confirmed this by mathematical simulation. Collectively, we propose a way to understand angiogenesis, based on unique EC behavioral properties that are partially dependent on VE-cadherin function.

Keywords: Cell biology; Mathematical biosciences.

Associated data

figshare/10.6084/m9.figshare.21952793