Department of Materials, and Institute for Biomedical Engineering, Imperial College London , London, UK, SW7 2AZ.
J Am Chem Soc. 2011 Feb 9;133(5):1438-50. doi: 10.1021/ja108285u. Epub 2011 Jan 5.
Monolayer-protected metal nanoparticles (MPMNs) are a newly discovered class of nanoparticles with an ordered, striped domain structure that can be readily manipulated by altering the ratio of the hydrophobic to hydrophilic ligands. This property makes them uniquely suited to systematic studies of the role of nanostructuring on biomolecule adsorption, a phenomenon of paramount importance in biomaterials design. In this work, we examine the interaction of the simple, globular protein cytochrome C (Cyt C) with MPMN surfaces using experimental protein assays and computational molecular dynamics simulations. Experimental assays revealed that adsorption of Cyt C generally increased with increasing surface polar ligand content, indicative of the dominance of hydrophilic interactions in Cyt C-MPMN binding. Protein-surface adsorption enthalpies calculated from computational simulations employing rigid-backbone coarse-grained Cyt C and MPMN models indicate a monotonic increase in adsorption enthalpy with respect to MPMN surface polarity. These results are in qualitative agreement with experimental results and suggest that Cyt C does not undergo significant structural disruption upon adsorption to MPMN surfaces. Coarse-grained and atomistic simulations furthermore elucidated the important role of lysine in facilitating Cyt C adsorption to MPMN surfaces. The amphipathic character of the lysine side chain enables it to form close contacts with both polar and nonpolar surface ligands simultaneously, rendering it especially important for interactions with surfaces composed of adjacent nanoscale chemical domains. The importance of these structural characteristics of lysine suggests that proteins may be engineered to specifically interact with nanomaterials by targeted incorporation of unnatural amino acids possessing dual affinity to differing chemical motifs.
单层保护金属纳米粒子（MPMNs）是一类新发现的纳米粒子，具有有序的条带畴结构，可以通过改变疏水性配体与亲水性配体的比例来轻易地操纵。这种特性使它们非常适合系统地研究纳米结构对生物分子吸附的作用，这在生物材料设计中是至关重要的现象。在这项工作中，我们使用实验蛋白质分析和计算分子动力学模拟来研究简单的球形蛋白细胞色素 C（Cyt C）与 MPMN 表面的相互作用。实验分析表明，Cyt C 的吸附通常随表面极性配体含量的增加而增加，表明亲水相互作用在 Cyt C-MPMN 结合中占主导地位。从使用刚性骨架粗粒 Cyt C 和 MPMN 模型的计算模拟中计算的蛋白质-表面吸附焓表明，吸附焓随 MPMN 表面极性单调增加。这些结果与实验结果定性一致，并表明 Cyt C 在吸附到 MPMN 表面时不会发生明显的结构破坏。粗粒和原子模拟进一步阐明了赖氨酸在促进 Cyt C 吸附到 MPMN 表面方面的重要作用。赖氨酸侧链的两亲性使其能够与极性和非极性表面配体同时形成紧密接触，使其对于与由相邻纳米级化学畴组成的表面的相互作用特别重要。赖氨酸这些结构特性的重要性表明，蛋白质可以通过靶向整合具有对不同化学基序具有双重亲和力的非天然氨基酸来专门与纳米材料相互作用。
