Mechanically primed cells transfer memory to fibrous matrices for invasion across environments of distinct stiffness and dimensionality.
Mechanically primed cells transfer memory to fibrous matrices for invasion across environments of distinct stiffness and dimensionality.
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DOI：
10.1091/mbc.e22-10-0469
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发表时间：
2023-05-15
影响因子：
3.3
通讯作者：
Pathak, Amit
中科院分区：
文献类型：
--
作者：
Almeida, Jose A.;Mathur, Jairaj;Lee, Ye Lim;Sarker, Bapi;Pathak, Amit
在整个发育和疾病发展过程中，细胞感知并在机械上不同的环境中迁移。然而，对过去环境的机械记忆是否使细胞能够导航新的三维细胞外基质仍不清楚。在这里，我们表明，与软质相比，硬质上的细胞产生更高水平的力量来重塑胶原纤维并促进侵袭。这种启动优势在致密或硬化的胶原蛋白中持续存在。我们通过一个基于晶格的模型来解释这种记忆依赖的、跨环境的细胞入侵，在该模型中，僵硬启动的细胞力重塑胶原蛋白，并将未来细胞入侵所需的能量降至最低。根据我们的模型，细胞通过胶原蛋白的排列和拉伸将其机械记忆转移到基质中，而这个重塑的基质通知未来的细胞侵袭。因此，充满记忆的细胞通过记忆的细胞矩阵转移，克服了对更软或更具挑战性的未来环境的机械感知。与模型预测一致，YES相关蛋白的耗尽破坏了侵袭前胶原重塑所需的细胞记忆的稳定。我们通过激光消融来释放胶原纤维中的张力，并通过抑制赖氨酰氧化酶来阻止纤维重塑，这两者都扰乱了记忆从细胞到基质的转移，并阻碍了跨环境的入侵。这些结果对癌症、纤维化和衰老有意义，在这些疾病中，潜在的细胞机械记忆从细胞到基质的转移可能会产生长期的细胞反应。
Cells sense and migrate across mechanically dissimilar environments throughout development and disease progression. However, it remains unclear whether mechanical memory of past environments empowers cells to navigate new, three-dimensional extracellular matrices. Here, we show that cells previously primed on stiff, compared with soft, matrices generate a higher level of forces to remodel collagen fibers and promote invasion. This priming advantage persists in dense or stiffened collagen. We explain this memory-dependent, cross-environment cell invasion through a lattice-based model wherein stiff-primed cellular forces remodel collagen and minimize energy required for future cell invasion. According to our model, cells transfer their mechanical memory to the matrix via collagen alignment and tension, and this remodeled matrix informs future cell invasion. Thus, memory-laden cells overcome mechanosensing of softer or challenging future environments via a cell–matrix transfer of memory. Consistent with model predictions, depletion of yes-associated protein destabilizes the cellular memory required for collagen remodeling before invasion. We release tension in collagen fibers via laser ablation and disable fiber remodeling by lysyl-oxidase inhibition, both of which disrupt cell-to-matrix transfer of memory and hamper cross-environment invasion. These results have implications for cancer, fibrosis, and aging, where a potential cell-to-matrix transfer of mechanical memory of cells may generate a prolonged cellular response.