Abstract
Chemotaxis is the biased movement of cells in the direction of chemical gradients. Cellular signal processing capacity has been thought to be important to cells’ chemotaxis behavior. However, it still remains elusive how cells sense and decipher multiple chemical cues. In this study, we test a hypothesis that the chemotaxis performance of cells is constrained by the capacity to “multitask.” Specifically, if the intracellular signal processing capacity to respond to multiple cues is saturated, the effect of chemoattractants become antagonistic rather than synergistic or even independent. We experimentally investigate the migratory behavior of two types of cancer cells under single and combined cues of chemoattractants – transforming growth factor-beta and epidermal growth factor. For both cell types, the results show that the combination of the two attractants suppresses the chemotactic performance of cancer cells. We propose a novel biophysical framework that puts forward the hypothesis that the antagonism is not because of crosstalk, but because of the saturation of the intracellular signal processing capacity. The theory predicts that the suppression of chemotactic performance can alternatively be caused by saturating the signal processing capacity with background signal strength. We confirm this prediction with further experiments on both cell lines. Our framework provides new insight into the intracellular mechanism of signal processing and allows one to predict cellular response under complex chemical cues.
Statement of Significance Cellular signal processing capacity is critical to understand cell chemotaxis behaviors — cell movement toward the direction of a chemical gradient signal. The signal environment exposing to cells is complex with multiple chemical cues. However, it is still elusive how cells sense and decipher multiple chemical signals. Here we experimentally investigate the chemotaxis performance of cells and propose a novel biophysical framework to reveal cells’ signal processing capacity to “multitask”. Is there a limit in the cellular multitasking capacity? We observe that overloaded environmental signal constraints chemotactic performance, specifically accuracy. Our results suggest that saturation of the signal processing capacity causes the suppression of the chemotactic accuracy. Our framework provides new insight into signal processing mechanisms to predict cellular response under complex chemical signals.
Competing Interest Statement
The authors have declared no competing interest.
