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

Autor: Yasha Sharma, Jacopo Ferruzzi, Muhammad H. Zaman, Jin-Ah Park, Yu Long Han, Jennifer A. Mitchel, Adil Khan, Zi Chen, Wenying Kang, Jeffrey J. Fredberg, Darren Roblyer, Catalina-Paula Spatarelu, Adrian F. Pegoraro, James P. Butler, Ming Guo, Stephan A. Koehler
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: iScience, Vol 24, Iss 11, Pp 103252-(2021)
iScience
ISSN: 2589-0042
Popis: 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.
Graphical abstract
Highlights • Tumor spheroids invading into a 3D matrix exhibit coexistent material phases • Invasion leads to spatiotemporal heterogeneities consistent with jamming dynamics • Phase separation patterns are captured by a model-based jamming phase diagram • Effective thermodynamic variables Teff and Pconf capture cell and matrix properties
Biophysics; Cancer; Mechanobiology
Databáze: OpenAIRE