Roles of Remote and Contact Forces in Epithelial Cell Structure Formation

Tadashi Nakano,Yutaka Okaie,Yasuha Kinugasa,Takako Koujin,Tatsuya Suda,Yasushi Hiraoka,Tokuko Haraguchi

doi:10.1016/j.bpj.2020.01.037

Tadashi Nakano, Yutaka Okaie + Show 5 more

Open Access

https://doi.org/10.1016/j.bpj.2020.01.037

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Abstract

Cancer cells collectively form a large-scale structure for their growth. In this article, we report that HeLa cells, epithelial-like human cervical cancer cells, aggressively migrate on Matrigel and form a large-scale structure in a cell-density-dependent manner. To explain the experimental results, we develop a simple model in which cells interact and migrate using the two fundamentally different types of force, remote and contact forces, and show how cells form a large-scale structure. We demonstrate that the simple model reproduces experimental observations, suggesting that the remote and contact forces considered in this work play a major role in large-scale structure formation of HeLa cells. This article provides important evidence that cancer cells form a large-scale structure and develops an understanding into the poorly understood mechanisms of their structure formation.

Highlights

How cells interact and form a large-scale structure is a longstanding question in biology
HeLa cells maintained their moving direction for a longer time period on a Matrigel layer than on a glass surface. On both thin and thick Matrigel layers, the temporal correlation function (TCF) of cell velocities gradually decreased over 5 h (50% decrease in 210 min on a thick Matrigel layer and in 170 min on a thin Matrigel layer), whereas on a glass surface, it decreased quickly (50% decrease in 40 min) (Fig. 1 D), showing that cell movements on Matrigel are more persistent and that those on a glass surface are more random
We observed that HeLa cells move aggressively on Matrigel and that HeLa cell motility depends on the Matrigel thickness

Summary

Introduction

How cells interact and form a large-scale structure is a longstanding question in biology. Human umbilical vein endothelial cells have been proposed to secrete vascular endothelial growth factors to create the vascular endothelial growth factor gradient in their environment and attract other cells at a distance [9] Another example of the remote force is the haptotactic force. Human umbilical vein endothelial cells and human microvascular endothelial cells directionally move on a surface of an adhesive substrate, such as the extracellular matrix (ECM), according to the adhesion gradient or the gradient of surface-bound molecules [12,13]. Another example of the remote force is the mechanotactic force.

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