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Abstract Accurately replicating and analyzing cellular responses to mechanical cues is vital for exploring metastatic disease progression. However, many of the existing in vitro platforms for applying mechanical stimulation seed cells on synthetic substrates. To better recapitulate physiological conditions, a novel actuating platform is developed with the ability to apply tensile strain on cells at various amplitudes and frequencies in a high‐throughput multi‐well culture plate using a physiologically relevant substrate. Suspending fibrillar fibronectin across the body of the magnetic actuator provides a matrix representative of early metastasis for 3D cell culture that is not reliant on a synthetic substrate. This platform enables the culturing and analysis of various cell types in an environment that mimics the dynamic stretching of lung tissue during normal respiration. Metabolic activity, YAP activation, and morphology of breast cancer cells are analyzed within one week of cyclic stretching or static culture. Further, matrix degradation is significantly reduced in breast cancer cell lines with metastatic potential after actuation. These new findings demonstrate a clear suppressive cellular response due to cyclic stretching that has implications for a mechanical role in the dormancy and reactivation of disseminated breast cancer cells to macrometastases.
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Pneumatic Non-Equibiaxial Cell Stretching Device With Live-Cell Imaging
Objective: Adherent cell behavior is influ- enced by a complex interplay of factors, including chemical and mechanical signals. In vitro experiments that mimic the mechanical environment experienced by cells in vivo are crucial for understanding cellular behavior and the progression of disease. In this study, we developed and validated a low-cost pneumatically-controlled cell stretcher with independent control of strain in two directions of a membrane, enabling unequal biaxial stretching and real- time microscopy during actuation. Methods: The stretch- ing was achieved by two independent pneumatic channels controlled by electrical signals. We used finite element simulations to compute the membrane’s strain field and particle tracking algorithms based on image processing techniques to validate the strain fields and measure the cell orientation and morphology. Results: The device can supply uniaxial, equibiaxial, and unequal biaxial stretching up to 15% strain in each direction at a frequency of 1Hz, with a strain measurement error of less than 1%. Through live cell imaging, we determined that distinct stretching patterns elicited differing responses and alterations in cell orientation and morphology, particularly in terms of cell length and area. Conclusion: The device successfully pro- vides a large, uniform, and variable strain field for cell experiments, while also enabling real-time, live cell imag- ing. Significance: This scalable, low-cost platform provides mechanical stimulation to cell cultures by independently controlling strains in two directions. This could contribute to a deeper understanding of cellular response to bio- realistic strains and could be useful for future in vitro drug testing platforms.
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- PAR ID:
- 10517195
- Publisher / Repository:
- IEEE Transactions on Biomedical Engineering
- Date Published:
- Journal Name:
- IEEE Transactions on Biomedical Engineering
- ISSN:
- 0018-9294
- Page Range / eLocation ID:
- 1 to 11
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1109/TBME.2023.3319013
