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Hang on tight: reprogramming the cell with microstructural cues

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Abstract

Cells interact intimately with complex microdomains in their extracellular matrix (ECM) and maintain a delicate balance of mechanical forces through mechanosensitive cellular components. Tissue injury results in acute degradation of the ECM and disruption of cell-ECM contacts, manifesting in loss of cytoskeletal tension, leading to pathological cell transformation and the onset of disease. Recently, microscale hydrogel constructs have been developed to provide cells with microdomains to form focal adhesion binding sites, which enable restoration of cytoskeletal tension. These synthetic anchors can recapitulate the complex 3D architecture of the native ECM to provide microtopographical cues. The mechanical deformation of proteins at the cell surface can activate signaling cascades to modulate downstream gene-level transcription, making this a unique materials-based approach for reprogramming cell behavior. An overview of the mechanisms underlying these mechanosensitive interactions in fibroblasts, stem and other cell types is provided to review their effects on cellular reprogramming. Recent investigations on the fabrication, functionalization and implementation of these materials and microtopographical features for drug testing and therapeutic applications are discussed.

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Acknowledgements

This work was supported by the National Institutes of Health (P01-HL062426 and R01-HL137209).

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  1. Department of Bioengineering and Therapeutic Sciences, University of California, 1700 4th St Rm 204, San Francisco, CA, 94158, USA

    Long V. Le & Tejal A. Desai

  2. Department of Bioengineering, University of Illinois, Chicago, 835 S. Wolcott, Chicago, IL, 60612, USA

    Michael A. Mkrtschjan

  3. Department of Physiology and Biophysics, University of Illinois, Chicago, 835 S. Wolcott, Chicago, IL, 60612, USA

    Brenda Russell

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Le, L.V., Mkrtschjan, M.A., Russell, B. et al. Hang on tight: reprogramming the cell with microstructural cues. Biomed Microdevices 21, 43 (2019). https://doi.org/10.1007/s10544-019-0394-9

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  • DOI: https://doi.org/10.1007/s10544-019-0394-9

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