Single Cells Can Resolve Graded Stimuli

Cells use signaling pathways as windows into the environment to gather information, transduce it into their interior, and use it to drive behaviors. MAPK (ERK) is a highly conserved signaling pathway in eukaryotes, directing multiple fundamental cellular behaviors such as proliferation, migration, and differentiation, making it one of few central hubs in the signaling circuitry of cells. Despite this versatility of behaviors, population-level measurements have reported low information content (<1 bit) relayed through the ERK pathway, rendering the population barely able to distinguish the presence or absence of stimuli. Here, we contrast the information transmitted by a single cell and a population of cells. Using a combination of optogenetic experiments, data analysis based on information theory, and numerical simulations, we quantify the amount of information transduced from the receptor to ERK, from responses to singular, brief, and sparse input pulses. We show that single cells are indeed able to resolve between graded stimuli, yielding over 2 bits of information, however showing a large population heterogeneity.