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Directing cell migration and organization via nanocrater-patterned cell-repellent interfaces

Nature Materials volume 14, pages 918–923 (2015)Cite this article

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Abstract

Although adhesive interactions between cells and nanostructured interfaces have been studied extensively1,2,3,4,5,6, there is a paucity of data on how nanostructured interfaces repel cells by directing cell migration and cell-colony organization. Here, by using multiphoton ablation lithography7 to pattern surfaces with nanoscale craters of various aspect ratios and pitches, we show that the surfaces altered the cells’ focal-adhesion size and distribution, thus affecting cell morphology, migration and ultimately localization. We also show that nanocrater pitch can disrupt the formation of mature focal adhesions to favour the migration of cells towards higher-pitched regions, which present increased planar area for the formation of stable focal adhesions. Moreover, by designing surfaces with variable pitch but constant nanocrater dimensions, we were able to create circular and striped cellular patterns. Our surface-patterning approach, which does not involve chemical treatments and can be applied to various materials, represents a simple method to control cell behaviour on surfaces.

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Figure 1: Nanoscale craters were fabricated by direct-write laser ablation lithography.
Figure 2: Nanocrater-patterned interfaces repel cell colonization.
Figure 3: Time-lapse phase-contrast images of NIH3T3 cells cultured on a spacing-gradient pattern.
Figure 4: Effect of nanocrater size on cell migration and formation of a cell-repellent zone.
Figure 5: Focal-adhesion size distribution correlates with migration descriptors.

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Acknowledgements

This work was supported by the National Institutes of Health grants GM085754 and HL096525. We thank Y. J. Kim of KIST Europe for QCM-D measurements. Talin constructs were kindly provided by D. Calderwood, Yale University.

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Author notes

  1. Hojeong Jeon and Sangmo Koo: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Mechanical Engineering, Laser Thermal Laboratory, University of California, Berkeley, California 94720, USA

    Hojeong Jeon, Sangmo Koo & Costas P. Grigoropoulos

  2. Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea

    Hojeong Jeon

  3. Department of Materials Science and Engineering, University of California, Berkeley, California 94720, USA

    Willie Mae Reese, Peter Loskill & Kevin E. Healy

  4. Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, California 94720, USA

    Peter Loskill & Kevin E. Healy

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  1. Hojeong Jeon
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Contributions

C.P.G., K.E.H. and H.J. conceived and designed the sample fabrication and cell-migration experiments; C.P.G. supervised the laser fabrication; K.E.H. supervised the biological experiments and analysis; H.J. and S.K. fabricated the samples, and performed the cell-adhesion and -migration experiments; S.K. and P.L. analysed cell migration; W.M.R. performed focal-adhesion experiments and analysis. H.J. and K.E.H. wrote the manuscript with discussions and improvements from all authors. C.P.G. and K.E.H. designed and financially supported the study.

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Correspondence to Costas P. Grigoropoulos or Kevin E. Healy.

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The authors declare no competing financial interests.

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Jeon, H., Koo, S., Reese, W. et al. Directing cell migration and organization via nanocrater-patterned cell-repellent interfaces. Nature Mater 14, 918–923 (2015). https://doi.org/10.1038/nmat4342

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