Cell deformability is an essential determinant for tissue-scale mechanical nature, such as fluidity and rigidity, and is thus crucial for tissue homeostasis and stable developmental processes. However, large-scale simulations of deformable cells have been restricted to those of polygonal-shaped cells, limiting our understanding of populations of arbitrarily deformable cells, such as mesenchymal, amoeboid cells, and nonconfluent epithelial cells. Here, we present an efficient approach for simulating large populations of nonpolygonally deformable cells with considerably higher computational efficiency than existing methods. Using the method, we demonstrate that the densely packed active cell population interacting via excluded volume interactions exhibits a fluid-to-fluid transition. An experimentally measurable index of topological defects, defined using the number of neighboring cells, is also proposed to characterize this transition. This study provides a flexible approach to tissue-scale cell population and a broader perspective on the biological fluid phases.

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