Wilson Christopher G, Sisco Patrick N, Gadala-Maria Francis A, Murphy Catherine J, Goldsmith Edie C
Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
Biomaterials. 2009 Oct;30(29):5639-48. doi: 10.1016/j.biomaterials.2009.07.011. Epub 2009 Jul 30.
Gold nanorods (AuNRs) have unique optical properties for numerous biomedical applications, but the interactions between AuNRs and proteins, particularly those of the extracellular matrix (ECM), are poorly understood. Here the effects of AuNRs on the self-assembly, mechanics, and remodeling of type I collagen gels were examined in vitro. AuNRs were modified with polyelectrolyte multilayers (PEMs) to minimize cytotoxicity, and AuNRs with different terminal polymer chemistries were examined for their interactions with collagen by turbidity assays, rheological tests, and microscopy. Gel contraction assays were used to examine the effects of the PEM-coated AuNRs on cell-mediated collagen remodeling. Polyanion-terminated AuNRs significantly reduced the lag (nucleation) phase of collagen self-assembly and significantly increased the dynamic shear modulus of the polymerized gels, whereas polycation-terminated AuNRs had no effect on the mechanical properties of the collagen. Both polyanion- and polycation-terminated AuNRs significantly inhibited collagen gel contraction by cardiac fibroblasts, and the nanoparticles were localized in intra-, peri-, and extracellular compartments, suggesting that PEM-coated AuNRs influence cell behavior via multiple mechanisms. These results demonstrate the significance of nanoparticle-ECM interactions in determining the bioactivity of nanoparticles.
金纳米棒(AuNRs)在众多生物医学应用中具有独特的光学性质,但人们对AuNRs与蛋白质之间的相互作用,尤其是与细胞外基质(ECM)蛋白质的相互作用了解甚少。在此,我们在体外研究了AuNRs对I型胶原凝胶的自组装、力学性能和重塑的影响。用聚电解质多层膜(PEMs)对AuNRs进行修饰以将细胞毒性降至最低,并通过浊度测定、流变学测试和显微镜检查来研究具有不同末端聚合物化学性质的AuNRs与胶原蛋白的相互作用。采用凝胶收缩试验来研究PEM包被的AuNRs对细胞介导的胶原重塑的影响。聚阴离子封端的AuNRs显著缩短了胶原蛋白自组装的延迟(成核)阶段,并显著提高了聚合凝胶的动态剪切模量,而聚阳离子封端的AuNRs对胶原蛋白的力学性能没有影响。聚阴离子和聚阳离子封端的AuNRs均显著抑制心脏成纤维细胞引起的胶原凝胶收缩,并且纳米颗粒定位于细胞内、细胞周围和细胞外区域,这表明PEM包被的AuNRs通过多种机制影响细胞行为。这些结果证明了纳米颗粒与ECM相互作用在决定纳米颗粒生物活性方面的重要性。