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Position-dependent chemotactic response of slowly migrating cells in sigmoidal concentration profiles

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Abstract

Characterizing the chemotactic motility of slowly migrating cells as a function of time is still challenging. In this paper, we use a microfluidic device for investigating the chemotactic activity of HFF-1 fibroblasts in a sigmoidal concentration profile of epidermal growth factor (EGF). Sigmoidal concentration profiles are very common in biological systems but, in contrast to linear gradients, are much less studied in microfluidic systems. We monitored cell migration for up to 10 hours and found that chemotaxis is strongest where the absolute EGF concentration is below 25 pM (K D of EGF is 1 nM). Calculating the fraction of receptor occupancy (FRO) at the front and rear of the cells showed that the chemotactic activity of HFF-1 cells scaled with the difference in FRO between both ends of the cell normalized by the average FRO av of the cell. Interestingly, the mean chemotactic index of the cells was found to be a function of the gradient at the starting position and did not change when cells were entering into other regions of the highly non-linear concentration profile. Our studies demonstrate the usefulness of stable sigmoidal concentration profiles produced in microfluidic channels for a detailed analysis of the chemotactic response of slowly migrating cells.

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Acknowledgements

We acknowledge financial support by the German Federal Ministry of Education and Research (BMBF) under 03 12 02 3B and W4 00 37. We thank B. Morgenstern (IBMT) for cell culture assistance, S. Howitz (GeSiM, Grosserkmannsdorf, Germany) for support in chip processing, and Cetoni (Korbussen, Germany) for their valuable help.

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Authors and Affiliations

  1. Fraunhofer Institute for Biomedical Engineering (IBMT), Potsdam, Germany

    A. Renner, M. S. Jaeger & C. Duschl

  2. Roche Diagnostics AG, Rotkreuz, Switzerland

    A. Lankenau

Authors
  1. A. Renner
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  2. M. S. Jaeger
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  3. A. Lankenau
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  4. C. Duschl
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Correspondence to M. S. Jaeger.

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Renner, A., Jaeger, M.S., Lankenau, A. et al. Position-dependent chemotactic response of slowly migrating cells in sigmoidal concentration profiles. Appl. Phys. A 112, 637–645 (2013). https://doi.org/10.1007/s00339-012-7507-0

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  • DOI: https://doi.org/10.1007/s00339-012-7507-0

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