Interaction of Proteins with Functional Interfaces


Protein interactions with interfaces are crucial for understanding many bio-related chemical or physical processes. For example, one of the major difficulties with medical implants, such as hip replacement or cardiac stents, is that the body tries to reject them. A powerful immune response is triggered to fight the invasive implant; therefore the ways of preventing protein from binding to the implant are to be developed. This project aims to develop new methods to characterize the interactions and gain a comprehensive understanding of the phase behaviour in a typical soft matter system comprising proteins, nanoparticles and self-assembled monolayers (SAM) in solution. We intend to study the structure of SAMs, stability of colloid, protein adsorption and resistance behaviour in solution, with various parameters such as, the size of nanoparticles, the type of proteins, ionic strength and salt nature. The following questions will be addressed:

  • What is the conformation/structure adapted by thiol molecules or adsorbed proteins at various interfaces?
  • How to characterize the stability of functionalized nanoparticles and the kinetics of aggregation by a convenient method?
  • How do proteins interact with functionalized nanoparticles in solutions? What is the key parameter determining the phase behaviour of colloid-protein systems?

Protein resistance

Protein resistant OEG has attracted considerable attention due to its numerous applications in biotechnology and medical devices, whilst protein interactions are a key factor in determining the phase behaviour of biological systems. The majority of studies to date have been ex-situ and on flat surfaces. However, there are many interesting applications of functionalized gold colloids that may involve highly curved interfaces. For a mixture of proteins (BSA) and gold colloids, the protein-protein interaction changes little upon mixing with OEG SAM-decorated gold colloids. In contrast, the colloid-colloid interaction is found to be strongly dependent on the protein concentration and the size of the colloid itself. Adding protein to a colloidal solution results in an attractive depletion interaction between functionalized gold colloids, and above a critical protein concentration, the colloids form aggregates and flocculate. Adding salt to such mixtures enhances the depletion effect and decreases the critical protein concentration. The aggregation is a reversible process. The depletion interaction under various conditions is presented schematically in the following figure.


The time evolution of colloid flocculation due to the depletion interaction can be followed as shown in the following figure. After mixing with protein solution above a critical concentration the real time SAXS measurements indicate the appearance of a scattering maximum following a short induction time, which increases its intensity with time. However, the peak position does not change with time, protein concentration, and addition of salt. The peak corresponds to the distance of the nearest neighbour in the aggregates.

Currently, we are working on the following issues:

  • Structure of OEG SAMs on gold nanoparticles by small-angle scattering techniques
  • Interactions and phase behaviour of the mixture of protein with SAM- coated nanoparticles
  • Depletion-driven colloidal flocculation kinetics and structure studied by real time UV-visible spectroscopy and SAXS
  • Surface modification of metal colloids, such as charge, OEG thiol, protein absorption.


[1] F. Zhang, M. W. A. Skoda, R. M. J. Jacobs, R. A. Martin, C. M. Martin and F. Schreiber. Protein interactions studied by SAXS: effect of ionic strength and protein concentration for BSA in aqueous solutions. J. Phys. Chem. B. 2007, 111, 251.
[2] F. Zhang, M. W. A. Skoda, R. M. J. Jacobs, S. Zorn, R. A. Martin, C. M. Martin, G. F. Clark, G. Goerigk and F. Schreiber. Gold nanoparticles decorated with oligo(ethylene glycol) thiols: protein resistance and colloidal stability. J. Phys. Chem. A. 2007, 111, 12229.
[3] F. Zhang, D. G. Dresen, M. W. A. Skoda, R. M. J. C Jacobs, S. Zorn, R. A. Martin, C. M. Martin, G. F. Clark and F.Schreiber. Gold nanoparticles decorated with oligo(ethylene glycol) thiols: kinetics of colloid aggregation driven by depletion force. Eur. Biophys. J. 2008. 37, 551

For our recent work on proteins in solution, see list of publications.