Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 29, Pages 14448-14455Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1814271116
Keywords
mechanobiology; ECM microenvironment; optical tweezers; power law; cell and ECM rheology
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Funding
- Intramural Research Program of the National Institutes of Health, National Cancer Institute
- NATIONAL CANCER INSTITUTE [ZIABC011433] Funding Source: NIH RePORTER
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Mechanical homeostasis describes how cells sense physical cues from the microenvironment and concomitantly remodel both the cytoskeleton and the surrounding extracellular matrix (ECM). Such feedback is thought to be essential to healthy development and maintenance of tissue. However, the nature of the dynamic coupling between microscale cell and ECM mechanics remains poorly understood. Here we investigate how and whether cells remodel their cortex and basement membrane to adapt to their microenvironment. We measured both intracellular and extracellular viscoelasticity, generating a full factorial dataset on 5 cell lines in 2 ECMs subjected to 4 cytoskeletal drug treatments at 2 time points. Nonmalignant breast epithelial cells show a similar viscoelasticity to that measured for the local ECM when cultured in 3D laminin-rich ECM. In contrast, the malignant counterpart is stiffer than the local environment. We confirmed that other mammary cancer cells embedded in tissue-mimetic hydrogels are nearly 4-fold stiffer than the surrounding ECM. Perturbation of actomyosin did not yield uniform responses but instead depended on the cell type and chemistry of the hydrogel. The observed viscoelasticity of both ECM and cells were well described by power laws in a frequency range that governs single filament cytoskeletal dynamics. Remarkably, the intracellular and extracellular power law parameters for the entire dataset collectively fall onto 2 parallel master curves described by just 2 parameters. Our work shows that tumor cells are mechanically plastic to adapt to many environments and reveals dynamical scaling behavior in the microscale mechanical responses of both cells and ECM.
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