Chester Beatty Laboratories , Institute for Cancer Research , London SW3 6JB , U.K.
Department of Bioengineering and Institute for Bioengineering and Biosciences , Instituto Superior Técnico, Universidade de Lisboa , 1649-004 Lisbon , Portugal.
ACS Nano. 2019 Mar 26;13(3):2913-2926. doi: 10.1021/acsnano.8b06998. Epub 2019 Mar 4.
Biomaterial substrates can be engineered to present topographical signals to cells which, through interactions between the material and active components of the cell membrane, regulate key cellular processes and guide cell fate decisions. However, targeting mechanoresponsive elements that reside within the intracellular domain is a concept that has only recently emerged. Here, we show that mesoporous silicon nanoneedle arrays interact simultaneously with the cell membrane, cytoskeleton, and nucleus of primary human cells, generating distinct responses at each of these cellular compartments. Specifically, nanoneedles inhibit focal adhesion maturation at the membrane, reduce tension in the cytoskeleton, and lead to remodeling of the nuclear envelope at sites of impingement. The combined changes in actin cytoskeleton assembly, expression and segregation of the nuclear lamina, and localization of Yes-associated protein (YAP) correlate differently from what is canonically observed upon stimulation at the cell membrane, revealing that biophysical cues directed to the intracellular space can generate heretofore unobserved mechanosensory responses. These findings highlight the ability of nanoneedles to study and direct the phenotype of large cell populations simultaneously, through biophysical interactions with multiple mechanoresponsive components.
生物材料基质可以被设计成向细胞呈现形貌信号，通过材料与细胞膜活性成分之间的相互作用，调节关键的细胞过程并指导细胞命运决定。然而，靶向细胞内域中的机械响应元件是一个最近才出现的概念。在这里，我们表明介孔硅纳米针阵列与原代人细胞的细胞膜、细胞骨架和核同时相互作用，在这些细胞区室中的每一个都产生不同的反应。具体而言，纳米针抑制细胞膜上的粘着斑成熟，减少细胞骨架中的张力，并导致在撞击部位的核膜重塑。肌动蛋白细胞骨架组装的变化、核纤层的表达和分离以及 Yes 相关蛋白 (YAP) 的定位与在细胞膜上受到刺激时通常观察到的情况不同，这表明针对细胞内空间的生物物理线索可以产生迄今为止尚未观察到的机械感觉反应。这些发现强调了纳米针通过与多个机械响应组件的生物物理相互作用，同时研究和指导大细胞群体表型的能力。
