Signal processing capacity of the cellular sensory machinery regulates the accuracy of chemotaxis under complex cues

Abstract

HighlightsCellular sensory machinery can sense and decipher multiple chemical cues simultaneously Combination of TGF-b and EGF suppresses the chemotactic accuracy of cancer cells Cells have the physical capacity in signal processing with the shared pathway The saturation of the shared pathway can disturb the cells' accurate chemotaxis

Cells function as a ternary logic gate to decide migration direction under integrated chemical and fluidic cues

“…To evaluate the effect of the integrated chemical and fluidic cues, we engineer the cellular microenvironment by using a microfluidic platform having a center and two side channels [38,47]. A center channel contains cells embedded in a type I collagen mixture in the platform, where two adjacent source and sink channels are filled with the medium.…”

“…In order to quantify the cellular directional accuracy to an environmental cue, we use a directional accuracy index (DAI; see Materials and methods) as defined in Figure 1B. Here, we note that the DAI distribution of the control is concentrated at the extremes of -1 and 1, this is an expected and well-known consequence of the cosine in its definition, as a uniform distribution of angles produce a nonuniform distribution of cosines that is more concentrated at the extremes [38,47,50,51].…”

“…KIC is a murine pancreatic cancer cell line isolated from genetically engineered mouse model for pancreatic adenocarcinoma in which Kras was combined with deletion of the Ink4a locus (Ink4a/Arf L/L ). [70][71][72] The KIC cells showed mesenchymal phenotype in response to TGF-β, whose invasion potential increased and directed migration was induced [38,48]. These cells were cultured in RPMI 1640 with 2.05mM L-glutamine (GE Healthcare Bio-Sciences Corp., MA, USA) supplemented by 5% v/v fetal bovine serum (FBS) and 100 µg ml −1 penicillin/streptomycin (P/S).…”

“…In many cases, exposing cancer cells to two growth factors showed a synergistic effect on cell motility [32-35]. When one of the growth factors stimulates cells in the form of gradient, the other can have either a synergistic [36,37] or antagonistic [38] effect on directional accuracy or motility for directional migration. While the synergistic combination of the chemical cues was shown from the cooperative effect of their downstream pathways [39,40], antagonistic results were illustrated with cells’ signal-processing capacity [38].…”

“…When one of the growth factors stimulates cells in the form of gradient, the other can have either a synergistic [36,37] or antagonistic [38] effect on directional accuracy or motility for directional migration. While the synergistic combination of the chemical cues was shown from the cooperative effect of their downstream pathways [39,40], antagonistic results were illustrated with cells’ signal-processing capacity [38]. The cell’s ability to sense and process multiple chemical cues simultaneously has been physically modeled to predict limits of the cellular ability [41,42] or to distinguish one chemical from another [43-45].…”