The adhesion morphology of a cell monolayer results in a mechanical force inside cells, between cells, or between cells and substrates. The mechanical force regulates the differentiation of stem cells, but its influence on cell fusion is seldom studied. The present study is focused on osteoclast precursors, RAW264.7 monocytes, which can fuse into multinucleated cells (MNCs) responsible for bone resorption. Cells were cultured on circular and ring-like patterned substrates. Then, cell fusion, cell–substrate traction force, and force-sensitive molecules in different regions were measured and analyzed. Results showed that MNCs mainly appeared in the interior of the ring-like pattern and the central zone of the circular pattern, where both cell–substrate traction force and in-plane maximal shear stress were smaller than that at the patterns’ edge. The immunostaining results revealed that F-actin, vinculin, β-catenin, and E-cadherin were highly distributed at the edge of patterns. High seeding density of cells promoted mechanical force-dependent fusion. When calcium-dependent cell–cell connections were inhibited by E-cadherin antibody or low-calcium medium, the fusion into MNCs was greatly reduced. Thus, the morphology of cell monolayer decides the mechanical state of cell–substrate interaction and cell–cell connection, ultimately regulating the fusion of osteoclast precursors.

中文翻译：

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细胞-基质牵引力通过细胞-细胞相互作用调节破骨细胞前体的融合。

细胞单层的粘附形态导致细胞内部，细胞之间或细胞与底物之间的机械力。机械力调节干细胞的分化，但很少研究其对细胞融合的影响。本研究的重点是破骨细胞前体RAW264.7单核细胞，它们可以融合到负责骨吸收的多核细胞（MNC）中。将细胞培养在圆形和环状图案化底物上。然后，测量并分析了不同区域的细胞融合，细胞底物牵引力和力敏分子。结果表明，跨国公司主要出现在环形图案的内部和圆形图案的中央区域，其中单元基板的牵引力和面内最大剪切应力均小于图案边缘。免疫染色结果显示，F-肌动蛋白，纽蛋白，β-连环蛋白和E-钙粘蛋白高度分布在图案的边缘。细胞的高接种密度促进了机械力依赖性融合。当钙依赖的细胞间连接被E-cadherin抗体或低钙培养基抑制时，与MNC的融合将大大减少。因此，细胞单层的形态决定了细胞-底物相互作用和细胞-细胞连接的机械状态，最终调节破骨细胞前体的融合。与跨国公司的融合大大减少了。因此，细胞单层的形态决定了细胞-底物相互作用和细胞-细胞连接的机械状态，最终调节破骨细胞前体的融合。与跨国公司的融合大大减少了。因此，细胞单层的形态决定了细胞-底物相互作用和细胞-细胞连接的机械状态，最终调节破骨细胞前体的融合。