Journal
SCIENCE ADVANCES
Volume 7, Issue 8, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abe1969
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Funding
- National Science Foundation [PHY-1707751, CBET-2033302]
- National Institutes of Health [R01-EB027171]
- Stanford Bio-X Bowes Graduate Fellowship program
- National Science Foundation Graduate Research Fellowship Program
- Stanford Graduate Fellowship
- Stanford Bio-X Undergraduate Summer Research program
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Living tissues are a unique class of hybrid materials where active and thermal forces are closely linked. A new microrheology-based technique was developed to analyze the active and passive fluctuations of the extracellular matrix (ECM) in 3D cell culture models, revealing a dual mechanism of active stiffening and fluidization in breast cancer spheroids. This hybrid dynamics are tightly connected with invasion and suggest a reconciling mechanism for seemingly contradictory requirements in the ECM during invasion by breast cancer cells.
Living tissues embody a unique class of hybrid materials in which active and thermal forces are inextricably linked. Mechanical characterization of tissues demands descriptors that respect this hybrid nature. In this work, we develop a microrheology-based force spectrum analysis (FSA) technique to dissect the active and passive fluctuations of the extracellular matrix (ECM) in three-dimensional (3D) cell culture models. In two different stromal models and a 3D breast cancer spheroid model, our FSA reveals emergent hybrid dynamics that involve both high-frequency stress stiffening and low-frequency fluidization of the ECM. We show that this is a general consequence of nonlinear coupling between active forces and the frequency-dependent viscoelasticity of stress-stiffening networks. In 3D breast cancer spheroids, this dual active stiffening and fluidization is tightly connected with invasion. Our results suggest a mechanism whereby breast cancer cells reconcile the seemingly contradictory requirements for both tension and malleability in the ECM during invasion.
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