Mechanically competitive regulation of cell volume in cytoplasm-sharing cells connected by intercellular bridges

Abstract In multicellular organisms, various cellular structures exhibit cytoplasmic sharing, where cells remain interconnected. While essential for development and function in contexts such as germ cell formation and insect early embryos, the physical basis of cell volume regulation in these systems remains poorly defined. Germline cysts are formed by interconnected sister cells via intercellular bridges. In mice, germline cysts form during gametogenesis in fetal ovaries and testes. In mouse fetal female cysts, cells with numerous bridges preferentially differentiate into oocytes by selectively increasing their volume, a process that may be mediated through cytoplasmic flow. This volume bias may be influenced by hydrostatic pressure within the cytoplasm. Here, we theoretically investigate how the mechanical properties of cells affect cytoplasmic pressure and volume distribution within interconnected cells. Our soap-bubble model revealed that cells with more bridges exhibit increased volume when they have large cell-cell contact areas, as observed in fetal cysts. We found that incorporating cell cycle (including cell growth and cell division) significantly enhances the likelihood of volume bias in favor of cells with more bridges. These theoretical findings suggest that intrinsic mechanical properties, coupled with cell cycle, establish robust cyst development in fetal female germline cysts. Our findings also provide insights into the volume dynamics observed in adult male germline cysts, which are characterized by smaller cell-cell contact areas. Impact statement A theoretical model demonstrates how mechanical properties and cell cycle dynamics regulate volume distribution in germline cysts, providing a physical basis for oocyte differentiation.