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Computational reconstruction of cell and tissue surfaces for modeling and data analysis

Nature Protocols volume 4, pages 1006–1012 (2009)Cite this article

Abstract

We present a method for the computational reconstruction of the 3-D morphology of biological objects, such as cells, cell conjugates or 3-D arrangements of tissue structures, using data from high-resolution microscopy modalities. The method is based on the iterative optimization of Voronoi representations of the spatial structures. The reconstructions of biological surfaces automatically adapt to morphological features of varying complexity with flexible degrees of resolution. We show how 3-D confocal images of single cells can be used to generate numerical representations of cellular membranes that may serve as the basis for realistic, spatially resolved computational models of membrane processes or intracellular signaling. Another example shows how the protocol can be used to reconstruct tissue boundaries from segmented two-photon image data that facilitate the quantitative analysis of lymphocyte migration behavior in relation to microanatomical structures. Processing time is of the order of minutes depending on data features and reconstruction parameters.

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Figure 1: Iterative Voronoi mesh optimization illustrated in the 2-D plane.
Figure 2: Binary image generation from fluorescence microscopy data.
Figure 3: Illustration of Voronoi surface elements.
Figure 4: Optimizing surface reconstruction for a given number of vertices/elements (n = 500) for the T cell shown in Figure 2.
Figure 5: Automatic, adaptive surface reconstruction of the T-cell microscopy data shown in Figure 1, minimizing the required number of vertices/elements for a given reconstruction accuracy (ratio of out-of-plane/in-plane resolution 9:1, average cell radius ∼4.5 μm, compare the scale in Fig. 1).
Figure 6: Surface reconstruction of cell conjugates.
Figure 7: Extraction of and mask generation for germinal center (GC) region.

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Acknowledgements

This research was supported by the Intramural Research Program of NIAID, NIH.

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Authors and Affiliations

  1. Program in Systems Immunology and Infectious Disease Modeling, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Frederick Klauschen, Ronald N Germain & Martin Meier-Schellersheim

  2. Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Hai Qi, Jackson G Egen & Ronald N Germain

Authors
  1. Frederick Klauschen
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  2. Hai Qi
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  3. Jackson G Egen
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  4. Ronald N Germain
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  5. Martin Meier-Schellersheim
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Correspondence to Frederick Klauschen or Martin Meier-Schellersheim.

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Klauschen, F., Qi, H., Egen, J. et al. Computational reconstruction of cell and tissue surfaces for modeling and data analysis. Nat Protoc 4, 1006–1012 (2009). https://doi.org/10.1038/nprot.2009.94

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