Individual cells are smarter than scientists previously thought

Divide or not? Individual cells make their decisions much more autonomously than previously thought.

Cells make choices based not only on external signals such as growth factors, but also on information received from inside the cell.

Every day, humans make choices for themselves. To ensure that a decision appropriate to the situation is made, these decisions often involve combining a range of contextual cues. Our senses provide us with the wealth of knowledge we need to make decisions. They pick up certain details about our environment, such as visual and auditory information, which our brain combines to build a holistic perception. This is called multisensory or multimodal perception.

Cells consider their own state when making choices

Individual cells are no different from humans in this respect. They are constantly making critical decisions, like splitting or not. Therefore, researchers from the University of Zurich (UZH) have extended the concept of contextual and multimodal perception found in humans to individual cells. Surprisingly, scientists have discovered that individual cells make decisions much more autonomously than previously thought.

“Adequate decision-making by individual cells uses multimodal perception, allowing cells to integrate outside cues such as growth factors with information from inside the cell, such as the number of cell organelles. “, explains Lucas Pelkmans. Pelkmans is a professor in the Department of Molecular Life Sciences at UZH.

Sometimes these internal signals can override external stimuli: for example in tumours, where the actual state of some cells overrides treatment with anti-proliferative drugs, making them resistant to treatment. “This drug resistance 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 modifying them,” says Pelkmans.

Simultaneous analysis of dozens of proteins in millions of cells

To test whether cells decide based on contextual and multimodal perception the way humans do, the scientists had to simultaneously measure the activity of multiple signaling nodes – the cells’ outer sensors – as well as multiple potential signals from within. of the cell, such as the local environment and the number of cellular organelles. Everything had to be analyzed in individual cells and 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 light microscopy. fluorescence,” says Bernhard Kramer, the first author of the study.

The researchers found that the variability in the activities of individual sensors across cells is closely related to the variation in internal signals. For example, the abundance of mitochondria, the powerhouses of cells, fundamentally affects how an external stimulus is perceived by an individual cell. In addition, each sensor integrates different signals from inside the cell. When the researchers assessed an important decision of a single cell – whether to proliferate or remain quiescent during a growth stimulus – they found that cell choice was influenced by the perception of multiple sensors and was modulated by predictably by signals from the internal state of the cell.

Cells make intelligent decisions

“For any specific decision of a cell, all external signals and internal signals must be seen together. Individual cells are thus able to make appropriate decisions based on the context – and are therefore clearly smarter than previously thought,” says Ph.D. candidate Kramer.

Reference: “Multimodal Perception Links Cellular State to Decision Making in Individual Cells” by Bernhard A. Kramer, Jacobo Sarabia del Castillo, and Lucas Pelkmans, July 14, 2022, Science.
DOI: 10.1126/science.abf4062

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