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Microarray with Micro- and Nano-topographies Enables Identification of the Optimal Topography for Directing the Differentiation of Primary Murine Neural Progenitor Cells

Authors

  • Aung Aung Kywe Moe,

    1. Department of Bioengineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117576
    2. Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857
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  • Mona Suryana,

    1. The Mechanobiology Institute Singapore, Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411
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  • Guillaume Marcy,

    1. Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857
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  • Sandy Keat Lim,

    1. Department of Bioengineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117576
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  • Soneela Ankam,

    1. Department of Bioengineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117576
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  • Jerome Zhi Wen Goh,

    1. Department of Bioengineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117576
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  • Jing Jin,

    1. Department of Bioengineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117576
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  • Benjamin Kim Kiat Teo,

    1. Department of Bioengineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117576
    2. The Mechanobiology Institute Singapore, Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411
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  • Jaslyn Bee Khuan Law,

    1. Institute of Materials Research and Engineering (IMRE), A*STAR, 3, Research Link, Singapore 117602
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  • Hong Yee Low,

    1. Institute of Materials Research and Engineering (IMRE), A*STAR, 3, Research Link, Singapore 117602
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  • Eyleen L. K. Goh,

    1. Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857
    2. Departments of Surgery and Physiology, National University of Singapore, Singapore
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  • Michael P. Sheetz,

    1. The Mechanobiology Institute Singapore, Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411
    2. Department of Biological Sciences, National University of Singapore, Singapore
    3. Department of Biological Sciences, Columbia University, New York NY, USA
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  • Evelyn K. F. Yim

    Corresponding author
    1. Department of Bioengineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117576
    2. The Mechanobiology Institute Singapore, Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411
    • Department of Bioengineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117576.
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Abstract

During development and tissue repair, progenitor cells are guided by both biochemical and biophysical cues of their microenvironment, including topographical signals. The topographical cues have been shown to play an important role in controlling the fate of cells. Systematic investigation of topographical structures with different geometries and sizes under the identical experimental conditions on the same chip will enhance the understanding of the role of shape and size in cell–topography interactions. A simple customizable multi-architecture chip (MARC) array is therefore developed to incorporate, on a single chip, distinct topographies of various architectural complexities, including both isotropic and anisotropic features, in nano- to micrometer dimensions, with different aspect ratios and hierarchical structures. Polydimethylsiloxane (PDMS) replicas of MARC are used to investigate the influence of different geometries and sizes in neural differentiation of primary murine neural progenitor cells (mNPCs). Anisotropic gratings (2 μm gratings, 250 nm gratings) and isotropic 1 μm pillars significantly promote differentiation of mNPCs into neurons, as indicated by expression of β-III-tubulin (59%, 58%, and 58%, respectively, compared to 30% on the control). In contrast, glial differentiation is enhanced on isotropic 2 μm holes and 1 μm pillars. These results illustrate that anisotropic topographies enhance neuronal differentiation while isotropic topographies enhance glial differentiation on the same chip under the same conditions. MARC enables simultaneous cost-effective investigation of multiple topographies, allowing efficient optimization of topographical and biochemical cues to modulate cell differentiation.

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