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Biomedical Microdevices

, 17:30 | Cite as

Confinement dependent chemotaxis in two-photon polymerized linear migration constructs with highly definable concentration gradients

  • Gertrud Malene Hjortø
  • Mark Holm Olsen
  • Inge Marie Svane
  • Niels B. Larsen
Article

Abstract

Dendritic cell chemotaxis is known to follow chemoattractant concentration gradients through tissue of heterogeneous pore sizes, but the dependence of migration velocity on pore size and gradient steepness is not fully understood. We enabled chemotaxis studies for at least 42 hours at confinements relevant to tissue models by two-photon polymerization of linear channel constructs with cross-sections from 10 × 10 μm2 to 20 × 20 μm2 inside commercially available chemotaxis analysis chips. Faster directed migration was observed with decreasing channel dimensions despite substantial cell deformation in the narrower channels. Finite element modeling of a cell either partly or fully obstructing chemokine diffusion in the narrow channels revealed strong local accentuation of the chemokine concentration gradients. The modeled concentration differences across a cell correlated well with the observed velocity dependence on channel cross-section. However, added effects due to spatial confinement could not be excluded. The design freedom offered by two-photon polymerization was exploited to minimize the accentuated concentration gradients in cell-blocked channels by introducing “venting slits” to the surrounding medium at a length scale too small (≤500 nm) for the cells to explore, thereby decoupling effects of concentration gradients and spatial confinement. Studies in slitted 10 × 10 μm2 channels showed significantly reduced migration speeds indistinguishable from speeds observed in unslitted 20 × 20 μm2 channel. This result agrees with model predictions of very small concentration gradient variations in slitted channels, thus indicating a strong influence of the concentration gradient steepness, not the channel size, on the directed migration velocity.

Keywords

Two-photon polymerization Microchannels Chemotaxis Dendritic cells Chemokine Finite element modeling 

Notes

Acknowledgments

We thank Dr. Esben Kjær Unmack Larsen for assistance with photochemical modification of chip surfaces with PEGDA. We acknowledge financial support from the Danish Council for Independent Research, Technology and Production Sciences, grant# 09-070021.

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Gertrud Malene Hjortø
    • 1
    • 3
  • Mark Holm Olsen
    • 1
  • Inge Marie Svane
    • 2
  • Niels B. Larsen
    • 1
  1. 1.Department of Micro- and NanotechnologyTechnical University of DenmarkKgs. LyngbyDenmark
  2. 2.Department of Haematology and Oncology, Center for Cancer Immune Therapy (CCIT)Copenhagen University Hospital at HerlevHerlevDenmark
  3. 3.Department of Neuroscience and PharmacologyUniversity of CopenhagenCopenhagenDenmark

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