Microrheology reveals simultaneous cell-mediated matrix stiffening and fluidization that underlie breast cancer invasion
- Resource Type
- Authors
- Pamela C. Cai; Audrey Zhu; Bauer L. LeSavage; Sarah C. Heilshorn; Andrew J. Spakowitz; Brad A. Krajina; Julien G Roth
- Source
- Science Advances
- Subject
- Microrheology
Stromal cell
Materials Science
Biophysics
Cell Culture Techniques
Breast Neoplasms
Matrix (biology)
Extracellular matrix
03 medical and health sciences
0302 clinical medicine
Humans
skin and connective tissue diseases
Research Articles
030304 developmental biology
0303 health sciences
Multidisciplinary
Chemistry
Mechanism (biology)
Viscosity
Dynamics (mechanics)
Spheroid
SciAdv r-articles
Stiffening
Extracellular Matrix
030220 oncology & carcinogenesis
Female
Research Article
- Language
- English
- ISSN
- 2375-2548
Invading breast cancer cells transform the mechanics of their surroundings across a panorama of time scales.
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.