Holt Brian D, Shams Hengameh, Horst Travis A, Basu Saurav, Rape Andrew D, Wang Yu-Li, Rohde Gustavo K, Mofrad Mohammad R K, Islam Mohammad F, Dahl Kris Noel
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
J Funct Biomater. 2012 May 23;3(2):398-417. doi: 10.3390/jfb3020398.
With a range of desirable mechanical and optical properties, single wall carbon nanotubes (SWCNTs) are a promising material for nanobiotechnologies. SWCNTs also have potential as biomaterials for modulation of cellular structures. Previously, we showed that highly purified, dispersed SWCNTs grossly alter F-actin inside cells. F-actin plays critical roles in the maintenance of cell structure, force transduction, transport and cytokinesis. Thus, quantification of SWCNT-actin interactions ranging from molecular, sub-cellular and cellular levels with both structure and function is critical for developing SWCNT-based biotechnologies. Further, this interaction can be exploited, using SWCNTs as a unique actin-altering material. Here, we utilized molecular dynamics simulations to explore the interactions of SWCNTs with actin filaments. Fluorescence lifetime imaging microscopy confirmed that SWCNTs were located within ~5 nm of F-actin in cells but did not interact with G-actin. SWCNTs did not alter myosin II sub-cellular localization, and SWCNT treatment in cells led to significantly shorter actin filaments. Functionally, cells with internalized SWCNTs had greatly reduced cell traction force. Combined, these results demonstrate direct, specific SWCNT alteration of F-actin structures which can be exploited for SWCNT-based biotechnologies and utilized as a new method to probe fundamental actin-related cellular processes and biophysics.
单壁碳纳米管（SWCNTs）具有一系列理想的机械和光学特性，是纳米生物技术领域一种很有前景的材料。SWCNTs作为调节细胞结构的生物材料也具有潜力。此前，我们发现高度纯化、分散的SWCNTs会显著改变细胞内的F-肌动蛋白。F-肌动蛋白在维持细胞结构、力转导、运输和胞质分裂中发挥着关键作用。因此，从分子、亚细胞和细胞水平对SWCNT-肌动蛋白相互作用进行结构和功能方面的量化，对于开发基于SWCNT的生物技术至关重要。此外，可以利用这种相互作用，将SWCNTs作为一种独特的能改变肌动蛋白的材料。在此，我们利用分子动力学模拟来探索SWCNTs与肌动蛋白丝的相互作用。荧光寿命成像显微镜证实，SWCNTs在细胞中位于F-肌动蛋白约5纳米范围内，但不与G-肌动蛋白相互作用。SWCNTs不会改变肌球蛋白II的亚细胞定位，并且对细胞进行SWCNT处理会导致肌动蛋白丝显著缩短。在功能上，内化了SWCNTs的细胞的细胞牵引力大大降低。综合来看，这些结果表明SWCNTs对F-肌动蛋白结构有直接、特异性的改变，这可用于基于SWCNT的生物技术，并作为一种探测与肌动蛋白相关的基本细胞过程和生物物理学的新方法。
