Deconstructing the third dimension - how 3D culture microenvironments alter cellular cues

Advance Online Publication July 13, 2012 doi: 10.1242/?jcs.079509 July 1, 2012 J Cell Sci 125, 3015-3024. Brendon M. Baker and Christopher S. Chen*

Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, PA 19104, USA ?*Author for correspondence (chrischen{at}seas.upenn.edu) Much of our understanding of the biological mechanisms that underlie cellular functions, such as migration, differentiation and force-sensing has been garnered from studying cells cultured on two-dimensional (2D) glass or plastic surfaces. However, more recently the cell biology field has come to appreciate the dissimilarity between these flat surfaces and the topographically complex, three-dimensional (3D) extracellular environments in which cells routinely operate in vivo. This has spurred substantial efforts towards the development of in vitro 3D biomimetic environments and has encouraged much cross-disciplinary work among biologists, material scientists and tissue engineers. As we move towards more-physiological culture systems for studying fundamental cellular processes, it is crucial to define exactly which factors are operative in 3D microenvironments. Thus, the focus of this Commentary will be on identifying and describing the fundamental features of 3D cell culture systems that influence cell structure, adhesion, mechanotransduction and signaling in response to soluble factors, which – in turn – regulate overall cellular function in ways that depart dramatically from traditional 2D culture formats. Additionally, we will describe experimental scenarios in which 3D culture is particularly relevant, highlight recent advances in materials engineering for studying cell biology, and discuss examples where studying cells in a 3D context provided insights that would not have been observed in traditional 2D systems.

Key words Funding

This work was supported in part from grants from the NIH [grant numbers EB00262, EB08396, HL73305, GM74048] and Center for Engineering Cells and Regeneration of the University of Pennsylvania. B.M.B. acknowledges financial support from a Ruth L. Kirschstein National Research Service Award. Deposited in PMC for release after 12 months.

This article is part of a Minifocus on Mechanotransduction. For further reading, please see related articles: ‘Finding the weakest link – exploring integrin-mediated mechanical molecular pathways’ by Pere Roca-Cusachs et al. (J. Cell Sci. 125, 3025-3038). ‘Signalling through mechanical inputs – a coordinated process’ by Huimin Zhang and Michel Labouesse (J. Cell Sci. 125, 3039-3049). ‘United we stand – integrating the actin cytoskeleton and cell–matrix adhesions in cellular mechanotransduction’ by Ulrich S. Schwarz and Margaret L. Gardel (J. Cell Sci. 125, 3051-3060). ‘Mechanosensitive mechanisms in transcriptional regulation’ by Akiko Mammoto et al. (J. Cell Sci. 125, 3061-3073). ‘Molecular force transduction by ion channels – diversity and unifying principles’ by Sergei Sukharev and Frederick Sachs (J. Cell Sci. 125, 3075-3083).

© 2012. Published by The Company of Biologists Ltd

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