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Fabrication of reconfigurable protein matrices by cracking

Nature Materials volume 4, pages 403–406 (2005)Cite this article

Abstract

The interface between extracellular matrices and cells is a dynamic environment that is crucial for regulating important cellular processes such as signal transduction, growth, differentiation, motility and apoptosis1. In vitro cellular studies and the development of new biomaterials would benefit from matrices that allow reversible modulation of the cell adhesive signals at a scale that is commensurate with individual adhesion complexes. Here, we describe the fabrication of substrates containing arrays of cracks in which cell-adhesive proteins are selectively adsorbed. The widths of the cracks (120–3,200 nm) are similar in size to individual adhesion complexes (typically 500–3,000 nm)2 and can be modulated by adjusting the mechanical strain applied to the substrate. Morphology of cells can be reversibly manipulated multiple times through in situ adjustment of crack widths and hence the amount of the cell-adhesive proteins accessible to the cell. These substrates provide a new tool for assessing cellular responses associated with exposure to matrix proteins.

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Figure 1: Schematic illustration of crack patterning.
Figure 2: Analysis of cracks.
Figure 3: Cyclic switching of cells between modes of spreading and retraction.

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Acknowledgements

We thank J. F. Mansfield and C. Wauchope for AFM assistance, S.-H. Chiang for the C2C12 cells, C. Chen for helpful discussions, D. P. Brereton for reviewing the article, BASF Corporation for kindly providing the PLURONIC F108 surfactant, and NIH (EB003793-01, PO1 AG20591), NSF (BES-0238625; DMI-0403603; CTS-0116331) and the NASA BioScience and Engineering Institute (NNC04AA21A) for funding.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Xiaoyue Zhu, Joong Hwan Bahng, Elizabeth Ho Liu, Jeongsup Shim & Shuichi Takayama

  2. Department of Mechanical Engineering, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Kristen L. Mills, Portia R. Peters & M. D. Thouless

  3. Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan

    Keiji Naruse

  4. Department of Anesthesiology, Emory University School of Medicine, Atlanta, 30322, Georgia, USA

    Marie E. Csete

  5. Department of Materials Science and Engineering, University of Michigan, Ann Arbor, 48109, Michigan, USA

    M. D. Thouless

  6. Macromolecular Science and Engineering Program, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Shuichi Takayama

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  1. Xiaoyue Zhu
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Correspondence to Shuichi Takayama.

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K.N. is co-founder of Strex. The other authors have no competing financial interests.

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Supplementary information and figures 1, 2, 3, 4 and 5 (PDF 605 kb)

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Zhu, X., Mills, K., Peters, P. et al. Fabrication of reconfigurable protein matrices by cracking. Nature Mater 4, 403–406 (2005). https://doi.org/10.1038/nmat1365

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