Abstract Cell development and behavior are driven by internal genetic programming, but the external microenvironment is increasingly recognized as a significant factor in cell differentiation, migration, and in the case of cancer, metastatic progression. Yet it remains unclear how the microenvironment influences cell processes, especially when examining cell motility. One factor that affects cell motility is cell mechanics, which is known to be related to substrate stiffness. Examining how cells interact with each other in response to mechanically differential substrates would allow an increased understanding of their coordinated cell motility. In order to probe the effect of substrate stiffness on tumor related cells in greater detail, we created hard–soft–hard (HSH) polydimethylsiloxane (PDMS) substrates with alternating regions of different stiffness (200 and 800 kPa). We then cultured WI-38 fibroblasts and A549 epithelial cells to probe their motile response to the substrates. We found that when the 2 cell types were exposed simultaneously to the same substrate, fibroblasts moved at an increased speed over epithelial cells. Furthermore, the HSH substrate allowed us to physically guide and separate the different cell types based on their relative motile speed. We believe that this method and results will be important in a diversity of areas including mechanical microenvironment, cell motility, and cancer biology.
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Controlled Glioma Cell Migration and Confinement Using Biomimetic‐Patterned Hydrogels
Cancer cell migration is significantly influenced by the physical properties (e.g., mechanics, topography) of the local extracellular matrix (ECM). However, how cells guide their movement in a complex, heterogeneous landscape while interpreting various physical factors, especially those with sizes on the subcellular length scale, is not completely understood. Herein, a photodegradable hydrogel is fabricated with control over the spatial distribution of features with different physical characteristics. On the surface of this hydrogel, patterns of features with sizes and spacings on the subcellular to cellular length scale are generated using a digital micromirror device, and the influence of the organization of these patterns on cellular migratory behavior is investigated. The size and spatial arrangement of hard (or stiff) and soft domains, more so than their topography, is found to have a significant impact on the migration speed. Using this approach, the maximum migration speed is observed on hydrogels with 10 μm pattern sizes spaced 10 μm apart. In this regime, the cells are confined and interact with both hard and soft regions at their periphery. Together, this study of cell–ECM interactions at the interface of hard and soft domains provides insights into how cancer cells interact with their environment.
- NSF-PAR ID:
- 10361355
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced NanoBiomed Research
- Volume:
- 2
- Issue:
- 1
- ISSN:
- 2699-9307
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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