细胞通过细胞外基质的机械聚类

中文摘要 AI 辅助

组织是活细胞和细胞外基质（ECM）的复合材料，它们共同决定了组织独特的力学行为。在这里，我们通过实验证明，收缩性细胞通过产生长程的、排列整齐且致密的纤维带重塑ECM，这些纤维带将细胞机械地耦合成多细胞簇。利用有限元模型，我们量化了由这些ECM带介导的、在不同细胞体积分数下的集体机械相互作用。该模型包含了模拟细胞主动力的收缩性颗粒，这些颗粒嵌入在非线性生物凝胶中，通过内部而非外部加载的方式诱导硬化。我们发现，即使是很小的收缩性颗粒体积分数（约10%），远低于球体接触渗流所预期的值，也会导致内部硬化，这种硬化由细胞间高浓度应力带介导，并且强烈依赖于ECM的非线性力学响应。对纤维带网络的渗流分析揭示了在临界颗粒体积分数处出现急剧转变，这与内部硬化的起始点一致。这些结果表明，收缩性细胞通过介质变形产生的长程相互作用有可能全局性地塑造块体凝胶的结构和力学性能，从而形成具有改性功能的结构。这些改性的宏观变化可以定义组织图案形成和形态发生中的组织原则。

英文摘要

Tissues are composites of living cells and extracellular matrix (ECM), that jointly determine their unique mechanical behavior. Here, we experimentally demonstrate that contractile cells remodel the ECM by generating long-range bands of aligned and densified fibers that mechanically couple cells into multicellular clusters. Using a finite-element model, we quantify the collective mechanical interactions mediated by these ECM bands for various volume fractions of cells. The model incorporates contractile particles that mimic cell-active forces within a nonlinear biological gel, inducing stiffening internally rather than through external loading. We find that even a small volume fraction of contractile particles (approximately 10%), much below what is expected for percolation of sphere contacts, leads to internal stiffening, mediated by the high-concentrated stress bands between cells and is strongly dependent on the nonlinear mechanical response of the ECM. Percolation analysis of the band network reveals sharp transitions at a critical particle volume fraction, that aligns with the onset of internal stiffening. These results demonstrate that long-range interaction between contractile cells through the deformation of the medium has the potential to globally shape the structure and mechanics of the bulk gel, leading to a functional structure with modified properties. These modified macroscopic changes can define organizing principles in tissue patterning and morphogenesis.

发表机构

• School of Mechanical Engineering, Tel Aviv University（特拉维夫大学机械工程学院）
• School of Chemistry, Tel Aviv University（特拉维夫大学化学学院）
• Advanced Materials and Liquid Crystal Institute, Kent State University（肯特州立大学先进材料与液晶研究所）
• Physics Department, Kent State University（肯特州立大学物理系）
• School of Physics and Astronomy, Tel Aviv University（特拉维夫大学物理与天文学院）
• Center for Physics and Chemistry of Living Systems, Tel Aviv University（特拉维夫大学生物系统物理与化学中心）
• Center for Computational Molecular and Materials Science, Tel Aviv University（特拉维夫大学计算分子与材料科学中心）
• International Institute for Sustainability with Knotted Chiral Meta Matter (WPI-SKCM 2 ), Hiroshima University（广岛大学国际可持续结型手性超物质研究所）

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