Mechanisms of endothelial cell coverage by pericytes: computational modelling of cell wrapping and in vitro experiments

Kei Sugihara, Saori Sasaki, Akiyoshi Uemura, Satoru Kidoaki, Takashi Miura

Research output: Contribution to journalArticle

Abstract

Pericytes (PCs) wrap around endothelial cells (ECs) and perform diverse functions in physiological and pathological processes. Although molecular interactions between ECs and PCs have been extensively studied, the morphological processes at the cellular level and their underlying mechanisms have remained elusive. In this study, using a simple cellular Potts model, we explored the mechanisms for EC wrapping by PCs. Based on the observed in vitro cell wrapping in three-dimensional PC-EC coculture, the model identified four putative contributing factors: preferential adhesion of PCs to the extracellular matrix (ECM), strong cell-cell adhesion, PC surface softness and larger PC size. While cell-cell adhesion can contribute to the prevention of cell segregation and the degree of cell wrapping, it cannot determine the orientation of cell wrapping alone. While atomic force microscopy revealed that PCs have a larger Young's modulus than ECs, the experimental analyses supported preferential ECM adhesion and size asymmetry. We also formulated the corresponding energy minimization problem and numerically solved this problem for specific cases. These results give biological insights into the role of PC-ECM adhesion in PC coverage. The modelling framework presented here should also be applicable to other cell wrapping phenomena observed in vivo.

Original languageEnglish
Article number20190739
Number of pages1
JournalJournal of the Royal Society, Interface
Volume17
Issue number162
DOIs
Publication statusPublished - Jan 1 2020

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Mechanisms of endothelial cell coverage by pericytes: computational modelling of cell wrapping and in vitro experiments'. Together they form a unique fingerprint.

  • Cite this