Confinement dependent chemotaxis in two-photon polymerized linear migration constructs with highly definable concentration gradients
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Confinement dependent chemotaxis in two-photon polymerized linear migration constructs with highly definable concentration gradients. / Hjorto, Gertrud Malene; Olsen, Mark Holm; Svane, Inge Marie; Larsen, Niels B.
I: Biomedical Microdevices, Bind 17, Nr. 2, 30, 04.2015, s. 1-10.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Confinement dependent chemotaxis in two-photon polymerized linear migration constructs with highly definable concentration gradients
AU - Hjorto, Gertrud Malene
AU - Olsen, Mark Holm
AU - Svane, Inge Marie
AU - Larsen, Niels B.
PY - 2015/4
Y1 - 2015/4
N2 - 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.
AB - 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.
KW - Two-photon polymerization
KW - Microchannels
KW - Chemotaxis
KW - Dendritic cells
KW - Chemokine
KW - Finite element modeling
U2 - 10.1007/s10544-015-9937-x
DO - 10.1007/s10544-015-9937-x
M3 - Journal article
C2 - 25681048
VL - 17
SP - 1
EP - 10
JO - Biomedical Microdevices
JF - Biomedical Microdevices
SN - 1387-2176
IS - 2
M1 - 30
ER -
ID: 160931282