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Let's reinvent cell culture.

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Mean elastic Young’s moduli of human organs



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Then now, let’s reinvent cell culture…

…with using soft, mechano-mimetic culture plates!

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  1. Discher DE et al. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005 310:1139.

  2. Bouchonville N et al. AFM mapping of the elastic properties of brain tissue reveals kPa/μm gradients of rigidity. Soft Matter. 2016 12:6232.

  3. Mammoto A et al. Mechanosensitive mechanisms in transcriptional regulation. J Cell Sci. 2012 125:3061.

  4. Tilghman RW et al. Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis.PLoS One. 2012 7(5):e37231.

  5. Missirlis D. The effect of substrate elasticity and actomyosin contractility on different forms of endocytosis. PLoS One. 2014 9(5):e96548.

  6. Park JS et al. Mechanical regulation of glycolysis via cytoskeleton architecture. Nature. 2020 578 :621-626

  7. Mouw JK et al. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat Med. 2014 20:360.

  8. Engler AJ et al. Matrix elasticity directs stem cell lineage specification. Cell. 2006 126(4):677-89.

  9. Zustiak SP. The Role of Matrix Compliance on Cell Responses to Drugs and Toxins: Towards Predictive Drug Screening Platforms. Macromol Biosci. 2015 15:589-99.​

In vitro cell-based assays are recognized as important contributors to persistent failures to translate promising drug candidates into clinical success, due, in part, to their limited predictability and reproducibility of the in vivo cell modelsIn biological conditions, cells organize in tissues with distinct physical properties where they evolve on soft and textured matrices [1]. Matrix rigidities impact almost all aspect of cell behavior [2]. including transcriptional regulation [3], protein synthesis [4], endocytosis [5]  and even glycolysis necessary for fast metabolism [6]They play a major role in carcinogenesis and metastasis formation [7], in stem cells differentiation [8] and in drug effectiveness [9]. Therefore, cell culture devices should not only allow cell survival and growth but must offer an environment as close as possible to the natural microenvironment of targeted tissues to be representative of the in vivo conditions.

Up to date, cell-based assays are still performed in plastic dishes, whose rigidity is up to one billion times stiffer than the in vivo cell environment! The failures of standard culture dishes to maintain the phenotype of many primary cells, or by appearing as wrong predictors support the evidence than these standard tools have now reached their limits.