Physical properties of cell-cell interactions have been suggested to be critical for the emergence of diverse three-dimensional morphologies of multicellular organisms. Their direct evaluation in living systems, however, has been difficult due to technical limitations. In this study, we developed a novel framework for analyzing and modeling the physical properties of cell-cell interactions. First, by analogy to molecular and colloidal sciences, cells were assumed to be particles, and the

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... ve forces and potentials of cell-cell interactions were statistically inferred from live imaging data. Next, the physical features of the potentials were analyzed. Finally, computational simulations based on these potentials were performed to test whether these potentials can reproduce the original morphologies. Our results from various systems, including Madin-Darby canine kidney (MDCK) cells, C.elegans early embryos, and mouse blastocysts, suggest that the method can accurately capture the diverse three-dimensional morphologies. Importantly, energy barriers were predicted to exist at the distant regions of the interactions, and this physical property was essential for formation of cavities, tubes, cups, and two-dimensional sheets. Collectively, these structures constitute basic structural units observed during morphogenesis and organogenesis. We propose that effective potentials of cell-cell interactions are parameters that can be measured from living organisms, and represent a fundamental principle underlying the emergence of diverse three-dimensional morphogenesis.