Title: Signal propagation in sensing and reciprocating cellular systems with spatial and structural heterogeneity,
Abstract: Sensing and reciprocating cellular systems (SARs) are important for the
operation of many biological systems. Production in interferon (IFN) SARs is
achieved through activation of the Jak-Stat pathway, and downstream
upregulation of IFN regulatory factor (IRF)-3 and IFN transcription, but the
role that high and low affinity IFNs play in this process remains unclear. We
present a comparative between a minimal spatio-temporal partial differential
equation (PDE) model and a novel spatio-structural-temporal (SST) model for the
consideration of receptor, binding, and metabolic aspects of SAR behaviour.
Using the SST framework, we simulate single- and multi-cluster paradigms of IFN
communication. Simulations reveal a cyclic process between the binding of IFN
to the receptor, and the consequent increase in metabolism, decreasing the
propensity for binding due to the internal feed-back mechanism. One observes
the effect of heterogeneity between cellular clusters, allowing them to
individualise and increase local production, and within clusters, where we
observe `sub popular quiescence'; a process whereby intra-cluster
subpopulations reduce their binding and metabolism such that other such
subpopulations may augment their production. Finally, we observe the ability
for low affinity IFN to communicate a long range signal, where high affinity
cannot, and the breakdown of this relationship through the introduction of cell
motility. Biological systems may utilise cell motility where environments are
unrestrictive and may use fixed system, with low affinity communication, where
a localised response is desirable.