caa a22 4500 605480265 CHVBK 20210128100414.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10544-015-9937-x doi (NATIONALLICENCE)springer-10.1007/s10544-015-9937-x Confinement dependent chemotaxis in two-photon polymerized linear migration constructs with highly definable concentration gradients [Elektronische Daten] [Gertrud Hjortø, Mark Olsen, Inge Svane, Niels Larsen] 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 42hours at confinements relevant to tissue models by two-photon polymerization of linear channel constructs with cross-sections from 10 × 10μm2 to 20 × 20μm2 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 (≤500nm) for the cells to explore, thereby decoupling effects of concentration gradients and spatial confinement. Studies in slitted 10 × 10μm2 channels showed significantly reduced migration speeds indistinguishable from speeds observed in unslitted 20 × 20μm2 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. Springer Science+Business Media New York, 2015 Two-photon polymerization nationallicence Microchannels nationallicence Chemotaxis nationallicence Dendritic cells nationallicence Chemokine nationallicence Finite element modeling nationallicence Hjortø Gertrud Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345E, 2800, Kgs. Lyngby, Denmark aut Olsen Mark Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345E, 2800, Kgs. Lyngby, Denmark aut Svane Inge Department of Haematology and Oncology, Center for Cancer Immune Therapy (CCIT), Copenhagen University Hospital at Herlev, 2730, Herlev, Denmark aut Larsen Niels Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345E, 2800, Kgs. Lyngby, Denmark aut Biomedical Microdevices Springer US; http://www.springer-ny.com 17/2(2015-04-01), 1-10 1387-2176 17:2<1 2015 17 10544 https://doi.org/10.1007/s10544-015-9937-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10544-015-9937-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hjortø Gertrud Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345E, 2800, Kgs. Lyngby, Denmark aut NATIONALLICENCE 700 1- Olsen Mark Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345E, 2800, Kgs. Lyngby, Denmark aut NATIONALLICENCE 700 1- Svane Inge Department of Haematology and Oncology, Center for Cancer Immune Therapy (CCIT), Copenhagen University Hospital at Herlev, 2730, Herlev, Denmark aut NATIONALLICENCE 700 1- Larsen Niels Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345E, 2800, Kgs. Lyngby, Denmark aut NATIONALLICENCE 773 0- Biomedical Microdevices Springer US; http://www.springer-ny.com 17/2(2015-04-01), 1-10 1387-2176 17:2<1 2015 17 10544