Centro di Ricerca Interdipartimentale sui Biomateriali, Università degli Studi di Napoli Federico II, 80125 Napoli, Italy.
Centro di Ricerca Interdipartimentale sui Biomateriali, Università degli Studi di Napoli Federico II, 80125 Napoli, Italy;
Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22004-22013. doi: 10.1073/pnas.1904660116. Epub 2019 Sep 30.
The ability of cells to perceive the mechanical identity of extracellular matrix, generally known as mechanosensing, is generally depicted as a consequence of an intricate balance between pulling forces actuated by the actin fibers on the adhesion plaques and the mechanical reaction of the supporting material. However, whether the cell is sensitive to the stiffness or to the energy required to deform the material remains unclear. To address this important issue, here the cytoskeleton mechanics of BALB/3T3 and MC3T3 cells seeded on linearly elastic substrates under different levels of deformation were studied. In particular, the effect of prestrain on cell mechanics was evaluated by seeding cells both on substrates with no prestrain and on substrates with different levels of prestrain. Results indicated that cells recognize the existence of prestrain, exhibiting a stiffer cytoskeleton on stretched material compared to cells seeded on unstretched substrate. Cytoskeleton mechanics of cells seeded on stretched material were, in addition, comparable to those measured after the stretching of the substrate and cells together to the same level of deformation. This observation clearly suggests that cell mechanosensing is not mediated only by the stiffness of the substrate, as widely assumed in the literature, but also by the deformation energy associated with the substrate. Indeed, the clutch model, based on the exclusive dependence of cell mechanics upon substrate stiffness, fails to describe our experimental results. By modifying the clutch model equations to incorporate the dependence on the strain energy, we were able to correctly interpret the experimental evidence.
细胞感知细胞外基质力学特性的能力，通常被称为力感受，通常被描绘为细胞骨架上的肌动蛋白纤维产生的拉力与支撑材料的力学反应之间复杂平衡的结果。然而，细胞是对材料的硬度敏感，还是对变形所需的能量敏感，目前仍不清楚。为了解决这个重要问题，我们研究了在不同变形水平下，种植在具有线性弹性的基底上的 BALB/3T3 和 MC3T3 细胞的细胞骨架力学。特别是，通过在没有预应变和具有不同预应力度的基底上种植细胞，评估了预应变对细胞力学的影响。结果表明，细胞能够识别预应变的存在，与种植在未拉伸基底上的细胞相比，在拉伸材料上的细胞骨架更加坚硬。此外，种植在拉伸材料上的细胞的细胞骨架力学与将基底和细胞一起拉伸到相同变形水平后的测量值相当。这一观察结果清楚地表明，细胞力感受不仅由基底的硬度介导，这在文献中被广泛假设，而且还由与基底相关的变形能介导。事实上，基于细胞力学仅依赖于基底硬度的离合器模型，无法描述我们的实验结果。通过修改离合器模型方程以纳入对应变能的依赖，我们能够正确解释实验证据。
