Are the effects of independent biophysical factors linearly additive? A 3D tumor migration model

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • Shanghai Jiao Tong University
  • Boston University

Abstract

Interstitial fluid flow plays a critical role in tumor cell invasion, yet this role has not been explored extensively in combination with other microenvironmental factors. Here, we establish a novel computational model of three-dimensional breast cancer cell migration to unveil the effect of interstitial fluid flow in the dependence of various extracellular matrix (ECM) physical properties. Our model integrates several principal factors: fluid dynamics, autologous chemotaxis, collagen fiber network structure, ECM stiffness, and cell-fiber and cell-flow interaction. First, independently with an aligned collagen fiber network and interstitial fluid flow, this model is validated by successfully reproducing the cell migration patterns. In the model, the interstitial fluid flow leads to directional symmetry breaking of chemotactic migration and synergizes with the ECM orientation to regulate cell migration. This synergy is universal in both the mesenchymal and the amoeboid migration modes, despite the fact that the cell-ECM interaction are different. Consequently, we construct a cell displacement function depending on these factors. Our cell migration model enables three-dimensional cancer migration prediction, mechanism exploration, and inhibition treatment design in a complex tumor microenvironment.

Bibliographic note

Available online 2nd October 2019

Details

Original languageEnglish
Pages (from-to)1702-1713
Number of pages12
JournalBiophysical Journal
Volume117
Issue number9
Early online date2 Oct 2019
Publication statusPublished - 5 Nov 2019

ASJC Scopus subject areas