A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

Wenying Kang; Jacopo Ferruzzi; Catalina-Paula Spatarelu; Yu Long Han; Yasha Sharma; Stephan A Koehler; Jennifer A Mitchel; Adil Khan; James P Butler; Darren Roblyer; Muhammad H Zaman; Jin-Ah Park; Ming Guo; Zi Chen; Adrian F Pegoraro; Jeffrey J Fredberg

doi:10.1016/j.isci.2021.103252

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

iScience. 2021 Oct 12;24(11):103252. doi: 10.1016/j.isci.2021.103252. eCollection 2021 Nov 19.

Authors

Wenying Kang¹, Jacopo Ferruzzi^{2

3}, Catalina-Paula Spatarelu⁴, Yu Long Han⁵, Yasha Sharma¹, Stephan A Koehler¹, Jennifer A Mitchel¹, Adil Khan³, James P Butler^{1

6}, Darren Roblyer², Muhammad H Zaman^{2

7}, Jin-Ah Park¹, Ming Guo⁵, Zi Chen⁴, Adrian F Pegoraro⁸, Jeffrey J Fredberg¹

Affiliations

¹ Department of Environmental Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
² Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
³ Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA.
⁴ Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
⁵ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁶ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁷ Howard Hughes Medical Institute, Boston University, Boston, MA 02115, USA.
⁸ Department of Physics, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

Abstract

It is well established that the early malignant tumor invades surrounding extracellular matrix (ECM) in a manner that depends upon material properties of constituent cells, surrounding ECM, and their interactions. Recent studies have established the capacity of the invading tumor spheroids to evolve into coexistent solid-like, fluid-like, and gas-like phases. Using breast cancer cell lines invading into engineered ECM, here we show that the spheroid interior develops spatial and temporal heterogeneities in material phase which, depending upon cell type and matrix density, ultimately result in a variety of phase separation patterns at the invasive front. Using a computational approach, we further show that these patterns are captured by a novel jamming phase diagram. We suggest that non-equilibrium phase separation based upon jamming and unjamming transitions may provide a unifying physical picture to describe cellular migratory dynamics within, and invasion from, a tumor.

Keywords: Biophysics; Cancer; Mechanobiology.

Abstract

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