Induced stepwise conformational change of human serum albumin on carbon nanotube surfaces Jia-Wei Shen, Tao Wu * , Qi Wang * , Yu Kang Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China article info Article history: Received 7 April 2008 Accepted 18 June 2008 Available online 9 July 2008 Keywords: Human serum albumin Carbon nanotube Protein adsorption Stepwise conformational change Protein-surface interaction abstract Non-covalent adsorption of proteins onto carbon nanotubes is important to understand the environ- mental and biological activity of carbon nanotubes as well as their potential applications in nano- structure fabrication. In this study, the adsorption dynamics and features of a model protein (the A sub-domain of human serum albumin) onto the surfaces of carbon nanotubes with different diameters were investigated out by molecular dynamics simulation. The adsorption behaviors were observed by both trajectory and quantitative analyses. During the adsorption process, the secondary structures of a- helices in the model protein were slightly affected. However, the random coils connecting these a-helices were strongly affected and this made the tertiary structure of protein change. The conformation and orientation selection of the protein were induced by the properties and the texture of surfaces indicated by the interaction curve. In addition, the stepwise adsorption dynamics of these processes are found. The mechanism of induced stepwise conformational change of protein on carbon nanotube surfaces would be helpful to better understand the protein–surface interaction at the molecular level. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Since the discovery of carbon nanotubes (CNTs) in 1991 [1], CNTs have raised considerable attention due to their fascinating structures and properties (electronic, optical, thermal, mechanical etc.) [2,3]. Recently, its potential application in biotechnology has attracted much interest, as CNTs have been reported to exhibit great advantages in biosensors [4,5], biomedical devices [6] and drug delivery systems (DDS) [7,8] etc. Pristine CNTs are highly hydrophobic, so the main obstacle in the utilization of CNTs in biological and medicinal chemistry is their poor solubility in aqueous-based biological milieu. Biomolecule functionalization is one option to overcome such defects. Many experimental efforts in this direction have been made through ei- ther covalent or non-covalent interactions between biomolecules and CNTs. For example, by covalently attaching functional groups to nanotubes, CNTs have been made soluble in different solvents [9– 11]. Through such modifications, the water solubility of CNTs is clearly improved and their biocompatibility profile completely transformed. However, sidewall or tip covalent functionalizations could alter the electronic structure of the nanotubes by disrupting the network of sp 2 -hybridized carbons [12] and/or change the potential energy surface of the CNT [13]. In addition to covalent functionalization, non-covalent bond functionalization is in- creasingly developed as an alternative route to keep the nanotubes’ intrinsic mechanical and electrical properties intact. It has been found that some proteins could be encapsulated into the inner space of CNTs [14–16], or non-covalently bound to the sidewalls of CNTs [17–19]. As for the non-covalent binding of peptides or pro- teins to the sidewall of CNTs, the processes all concern the ad- sorption and/or desorption of these molecules on the CNT surfaces [20–23]. Many experiments with varied methods were performed to qualitatively and quantitatively study the adsorption of peptides and/or proteins on the CNT surfaces. For example, by using the phage display technique, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Wang et al. [20] identified peptides with a selective affinity for CNTs. Their results of con- sensus binding sequences show a motif rich in histidine and tryp- tophan at specific locations, and the binding sequence is flexible, folding into a structure matching the geometry of CNTs. Witus et al. [21] created a series of peptides that individually dispersed CNTs with modifications to coat the nanotube in different environments. The ability of the peptides to individually disperse CNTs without altering their electronic structure is shown by visible and near-IR absorbance, fluorescence, and regular and vitreous ice cryo-TEM. Karajanagi et al. [22] examined the structure and function of two enzymes, a-chymotrypsin (CT) and soybean peroxidase (SBP), adsorbed onto carbon nanotubes. FT-IR spectroscopy revealed that both enzymes undergo structural changes upon adsorption, with substantial secondary structural perturbation observed for CT. The * Corresponding authors. Fax: þ86 571 87951895. E-mail addresses: tao_wu@zju.edu.cn (T. Wu), qiwang@zju.edu.cn (Q. Wang). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2008.06.013 Biomaterials 29 (2008) 3847–3855