A co-culture device with a tunable stiffness to understand combinatorial cell-cell and cell-matrix interactions

Cell behavior on 2-D in vitro cultures is continually being improved to better mimic in vivo physiological conditions by combining niche cues including multiple cell types and substrate stiffness, which are well known to impact cell phenotype. However, no system exists in which a user can systematic...

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Bibliographic Details
Published in:Integrative biology (Cambridge) 2013-01, Vol.5 (11), p.1344-1354
Main Authors: Rao, Nikhil, Grover, Gregory N, Vincent, Ludovic G, Evans, Samantha C, Choi, Yu Suk, Spencer, Katrina H, Hui, Elliot E, Engler, Adam J, Christman, Karen L
Format: Article
Language:English
Subjects:
Adipose Tissue - cytology
Adult
Cell Communication
Cell Culture Techniques - instrumentation
Cell Differentiation
Cell Membrane - metabolism
Cell Movement
Cell Proliferation
Coculture Techniques - instrumentation
Elastic Modulus
Equipment Design
Extracellular Matrix - metabolism
Gels - chemistry
Humans
Muscle Development
Myoblasts - cytology
Pressure
Silicon - chemistry
Stem Cells - cytology
Young Adult
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Summary:Cell behavior on 2-D in vitro cultures is continually being improved to better mimic in vivo physiological conditions by combining niche cues including multiple cell types and substrate stiffness, which are well known to impact cell phenotype. However, no system exists in which a user can systematically examine cell behavior on a substrate with a specific stiffness (elastic modulus) in culture with a different cell type, while maintaining distinct cell populations. We demonstrate the modification of a silicon reconfigurable co-culture system with a covalently linked hydrogel of user-defined stiffness. This device allows the user to control whether two separate cell populations are in contact with each other or only experience paracrine interactions on substrates of controllable stiffness. To illustrate the utility of this device, we examined the role of substrate stiffness combined with myoblast co-culture on adipose derived stem cell (ASC) differentiation and found that the presence of myoblasts and a 10 kPa substrate stiffness increased ASC myogenesis versus co-culture on stiff substrates. As this example highlights, this technology better controls the in vitro microenvironment, allowing the user to develop a more thorough understanding of the combined effects of cell-cell and cell-matrix interactions.
ISSN:1757-9694
1757-9708
DOI:10.1039/c3ib40078f