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Cells are the most elementary biotic entities that exhibit agentic purposive behaviors, as manifested by their remarkable ability to make decisions about their fate, including whether to proliferate or to die. For mammalian cells, these fundamental decision-making processes depend on direct cellular contact with their environment/tissue, and emerge from the ability of the cells to actively sense the physical properties of their environment – as opposed to its biochemical properties – and internally integrate the measurement outcomes upon reaching decisions.

The ultimate goal of the proposed project is to shed new light – in quantitative and measurable terms – on these fundamental purposive behaviors and to develop a conceptual framework to understand them, paying special attention to the spatiotemporal aspects of the underlying cellular processes. In particular, we will address the following fundamental questions:

How do active cellular measurements of the extracellular environment operate in space and time? What physical quantities are measured/sensed by cells, how these are translated into molecular-scale signals, and to what extent the molecular signals depend on the sensing machinery itself?
How does the integration over space and time of multiple inputs lead to a decision?

Our unique interdisciplinary collaboration, which has already led to a recent preliminary breakthrough, combines advanced experimental cell biology and theoretical physics of complex systems to address these pressing questions about the origin of purposive behaviors of cells, an essential first step for understanding biotic agentic behaviors. The project will lay down a conceptual and quantitative framework for understanding the emergence of cellular purposive behaviors. It is expected to lead to high-impact research articles and to the development of a larger-scale interdisciplinary research program.