Abstract：
In the process of tumorigenesis and development, cancer cells must integrate and respond to complex and dynamic signals in the tumor microenvironment. Nevertheless, simulating the original biomechanical and biochemical microenvironment of different cells in vitro is a fundamental challenge in studying synergistic effects. To address this issue, we have proposed a biomimetic multi-factor stimulation platform, which conveniently creates a two-dimensional matrix environment with controllable stiffness as biomechanical factor and can smoothly introduce biochemical cue. Our results indicated that the extracellular matrix (ECM) stiffness could enhance the cell stretching, which further lead to the amplification of cell-matrix adhesion and proliferation. And there existed obvious differences of endocytosis efficiency response of cells on matrix stiffness. Nanoparticles (NPs) with the same size and shape, but differs in electrical charges showed more uptake on harder matrix. Besides, the inorganic polyphosphates (polyP), which acts as energy storage and producer in the in-extracellular space, was proven to synergistically promote aforementioned cell biomechanical behaviors by increasing ATP metabolism for the first time. These results explored the impact of microenvironmental performance on the glioma mechanoresponses, and we believe this biomimetic multifactor stimulation method would exhibit a profound impact on researches of in vitro biomimetic cell culture and NPs-like drug phagocytosis.
摘要：
在肿瘤发生和发展的过程中，癌细胞必须整合和响应肿瘤微环境中复杂和动态的信号。然而，在体外模拟不同细胞的原始生物力学和生化微环境是研究协同作用的基本挑战。为了解决这个问题，我们提出了一种仿生多因素刺激平台，可以方便地创建具有可控刚度作为生物力学因子的二维矩阵环境，并且可以顺利地引入生化线索。我们的结果表明，细胞外基质（ECM）的刚度可以增强细胞的拉伸，这进一步导致细胞-基质粘附和增殖的放大。细胞内吞效率对基质硬度的反应存在明显差异。具有相同大小和形状的纳米颗粒(NPs),但不同的电荷显示更硬的基质吸收。此外,无机多磷酸盐(polyP)，在细胞外空间充当能量储存和生产者，首次证明通过增加ATP代谢协同促进上述细胞生物力学行为。这些结果探讨了微环境性能对神经胶质瘤机械反应的影响，我们相信这种仿生多因素刺激方法将对体外仿生细胞培养和类NPs药物吞噬作用的研究产生深远的影响。
