Individual Cells Are Apparently Pretty Smart

Researchers in Switzerland report findings that suggest individual human cells make decisions more autonomously than previously thought.

Like humans, single cells constantly make important decisions, such as whether to divide or not. Researchers at the University of Zurich (UZH) sought to apply the concept of multimodal perception—in which the human brain integrates sensory inputs like visual and auditory information to create a holistic perception—to cellular decision-making. 

Surprisingly, they found that single cells make decisions much more autonomously than previously thought. “Adequate decision-making by individual cells uses multimodal perception, allowing cells to integrate outside signals like growth factors with information from inside the cell, such as the number of cellular organelles,” says Lucas Pelkmans, professor at the Department of Molecular Life Sciences at UZH.

In certain situations, such inside cues can overrule the outside stimuli: e.g., in tumors, where the actual state of particular cells overrides the treatment with anti-proliferative drugs, thus making them treatment resistant. “Such resistance to drugs is a major problem in the fight against cancer. The solution may come from taking into account the contextual cues that individual cells experience and ultimately altering them,” Pelkmans says.

To test if cells decide according to contextual, multimodal perception as humans do, the researchers had to concurrently measure the activity of multiple signaling nodes—the cells’ outside sensors—as well as several potential cues from inside the cell, like the local environment and the number of cellular organelles. All of this had to be analyzed in single cells as well as across millions of cells. “To do this, we used ‘4i’, a method developed at UZH, which allows us to simultaneously visualize and quantify up to 80 different proteins and protein modifications in single cells using fluorescence microscopy,” says Bernhard Kramer, first author of the study.

The researchers found that the variability in the activities of individual sensors across cells is linked to variation in internal cues. For example, the abundance of mitochondria, the cells’ power stations, fundamentally affects how an external stimulus is perceived by a single cell. Furthermore, each sensor integrates different cues from inside the cell. When the researchers evaluated one important decision of a single cell—whether to proliferate or remain dormant in the presence of growth stimulus—they found that the cell’s choice was mediated by the perception of multiple sensors and was predictably modulated by cues of the cell’s internal state.

“For any specific decision of a cell, all outside signals and internal cues have to be viewed in concert. Single cells are thus able to make adequate context-dependent decisions—and are therefore clearly smarter than previously thought,” says Kramer.

The findings were published recently in Science.