Cells are the most basic entities exhibiting purposive behaviors, manifested by their remarkable ability to respond to their environment and make fate decisions, a prominent one is to proliferate or die. Understanding these in mammalian cells is essential in relation to fundamental phenomena such as embryonic development, aging and various diseases. Building on breakthroughs made in an ongoing JTF seed project, we hypothesize that cell-scale decision-making emerges from a fine interplay between the physical properties of the extracellular environment and the internal state of the cell, mediated by the unique active sensing capabilities of living cells. Our ultimate goal is developing a new paradigm for cellular decision-making within a spatiotemporal and dynamical perspective. We will address the following questions, among others:
What are the spatiotemporal dynamics accompanying active contractility and adhesion at early times during decision-making, under various external mechanical and geometrical conditions? How does the sensing machinery affect decision-making? Can one unify cellular proliferation and death decisions within a single mechanochemical framework? How do such decisions emerge from information integration over many sensing sites? Can one establish fate decision phase diagrams depending on external conditions and contractility inhibition? What are the principles of mechanically regulated cell death? Can one offer guidelines for fate decision reversal? How is decision-making altered in aging cells and fibrosis?
Our proven interdisciplinary collaboration, combining advanced experimental cell biology with theoretical physics of complex systems, is uniquely posed to address these and related questions in quantitative terms. It is expected to lay down a new conceptual and quantitative paradigm for understanding cellular fate decisions, accompanied by high-impact publications, and setting the foundations for a transformative longer-term research program.
