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Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

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Abstract

Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

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Acknowledgments

This work was initially funded by the EU-FP6 project NanoInteract (contract 033231) and was vitally inspired by the EU-FP7 project “Transkinetics”. Further support was received from the excellence cluster nanosystems initiative Munich (NIM) and the Center for NanoScience (CeNS). MPD gratefully acknowledges the Deutscher Akademischer Austausch Dienst for her Ph. D scholarship.

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Authors and Affiliations

  1. Faculty of Physics, Center for NanoScience, Ludwig-Maximilians University, Geschwister-Scholl-Platz 1, Munich, Germany

    M. P. D. Dobay, A. Piera Alberola, E. R. Mendoza & J. O. Rädler

  2. Department of Computer Science, University of the Philippines, Diliman, Quezon City, Philippines

    E. R. Mendoza

Authors
  1. M. P. D. Dobay
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  2. A. Piera Alberola
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  3. E. R. Mendoza
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  4. J. O. Rädler
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Correspondence to M. P. D. Dobay or J. O. Rädler.

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Dobay, M.P.D., Alberola, A.P., Mendoza, E.R. et al. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras. J Nanopart Res 14, 821 (2012). https://doi.org/10.1007/s11051-012-0821-9

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