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Covalently Immobilizing Interferon‑γ Drives Filopodia Production through Specific Receptor–Ligand Interactions Independently of Canonical Downstream Signaling
journal contribution
posted on 2020-05-11, 19:33 authored by Shaun
M. Christie, Trevor R. Ham, Grant T. Gilmore, Paul D. Toth, Nic D. Leipzig, Adam W. SmithImmobilizing
a signaling protein to guide cell behavior has been
employed in a wide variety of studies. This approach draws inspiration
from biology, where specific, affinity-based interactions between
membrane receptors and immobilized proteins in the extracellular matrix
guide many developmental and homeostatic processes. Synthetic immobilization
approaches, however, do not necessarily recapitulate the in
vivo signaling system and potentially lead to artificial
receptor–ligand interactions. To investigate the effects of
one example of engineered receptor–ligand interactions, we
focus on the immobilization of interferon-γ (IFN-γ), which
has been used to drive differentiation of neural stem cells (NSCs).
To isolate the effect of ligand immobilization, we transfected Cos-7
cells with only interferon-γ receptor 1 (IFNγR1), not
IFNγR2, so that the cells could bind IFN-γ but were incapable
of canonical signal transduction. We then exposed the cells to surfaces
containing covalently immobilized IFN-γ and studied membrane
morphology, receptor–ligand dynamics, and receptor activation.
We found that exposing cells to immobilized but not soluble IFN-γ
drove the formation of filopodia in both NSCs and Cos-7, showing that
covalently immobilizing IFN-γ is enough to affect cell behavior,
independently of canonical downstream signaling. Overall, this work
suggests that synthetic growth factor immobilization can influence
cell morphology beyond enhancing canonical cell responses through
the prolonged signaling duration or spatial patterning enabled by
protein immobilization. This suggests that differentiation of NSCs
could be driven by canonical and non-canonical pathways when IFN-γ
is covalently immobilized. This finding has broad implications for
bioengineering approaches to guide cell behavior, as one ligand has
the potential to impact multiple pathways even when cells lack the
canonical signal transduction machinery.
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growth factor immobilizationcovalently immobilizing IFN -γextracellular matrix guideCanonical Downstream Signaling ImmobilizingIFN -γcanonical signal transduction machineryguide cell behaviorIFN γRtransfected Cos -7 cellsSynthetic immobilization approachesinterferon -γ receptor 1NSCcanonical signal transductioncanonical cell responses
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