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
Affiliations
Wenying Kang
Department of Environmental Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Jacopo Ferruzzi
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA
Catalina-Paula Spatarelu
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA
Yu Long Han
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Yasha Sharma
Department of Environmental Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Stephan A. Koehler
Department of Environmental Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Jennifer A. Mitchel
Department of Environmental Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Adil Khan
Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA
James P. Butler
Department of Environmental Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Darren Roblyer
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
Muhammad H. Zaman
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Howard Hughes Medical Institute, Boston University, Boston, MA 02115, USA
Jin-Ah Park
Department of Environmental Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Ming Guo
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Zi Chen
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA
Adrian F. Pegoraro
Department of Physics, University of Ottawa, Ottawa, ON K1N 6N5, Canada
Jeffrey J. Fredberg
Department of Environmental Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Corresponding author
Summary: 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.
