Peptide adsorption on metal oxide surfaces. Investigating the biomaterial/biological interface with synchrotron radiation.
Lead Research Organisation:
University of Manchester
Department Name: Materials
Abstract
The interaction between biological molecules and inorganic material surfaces is of importance in a number of areas from biomedical devices for implantation, sensors and bioreactors. The required behaviours for each of these applications are slightly different, for example in biomedical implants it is thought that a protein conditioning layer is formed at the surface, prior to cell attachment and growth of new tissue. On the other hand, in pharmaceutical applications where protein therapeutics may be manufactured, interactions with the reactor material surfaces can lead to denaturation or agglomeration of the proteins. This may have the effect of removing the desired action protein, or in the worse case, causing unwanted side effects such as protein aggregation.
Studies of molecular adsorption on well-characterised surfaces using synchrotron techniques have led to an improved understanding of protein-metal interactions. However, in most cases the surface of a metal implant or pipeline will be terminated with a native oxide layer. In addition, these studies are often carried out under vacuum conditions, thus the effect of water on the adsorption process is not well understood. Obviously in a real biomedical device or pharmaceutical plant, water will be a major component of the surrounding media. Recent advances in photoelectron spectroscopy now allow measurements to be made in the presence of water and water vapour. Photoelectron spectroscopy is an extremely powerful probe of surface chemistry and the adsorption mechanism of molecules, since it is capable of studying just the top 1 - 10 nm of a material surface.
In this proposal we will study the adsorption processes of five different amino acids which exhibit varying degrees of acidity/basicity and two small peptides on idealised titanium dioxide surfaces. Rutile titanium dioxide is the native oxide formed on titanium which is widely used both as a metal and alloy in biomedical implants, and is believed to be a key factor in the success of these devices.
Studies of molecular adsorption on well-characterised surfaces using synchrotron techniques have led to an improved understanding of protein-metal interactions. However, in most cases the surface of a metal implant or pipeline will be terminated with a native oxide layer. In addition, these studies are often carried out under vacuum conditions, thus the effect of water on the adsorption process is not well understood. Obviously in a real biomedical device or pharmaceutical plant, water will be a major component of the surrounding media. Recent advances in photoelectron spectroscopy now allow measurements to be made in the presence of water and water vapour. Photoelectron spectroscopy is an extremely powerful probe of surface chemistry and the adsorption mechanism of molecules, since it is capable of studying just the top 1 - 10 nm of a material surface.
In this proposal we will study the adsorption processes of five different amino acids which exhibit varying degrees of acidity/basicity and two small peptides on idealised titanium dioxide surfaces. Rutile titanium dioxide is the native oxide formed on titanium which is widely used both as a metal and alloy in biomedical implants, and is believed to be a key factor in the success of these devices.
Planned Impact
The proposed work will determine the adsorption mechanism of some important amino acids and tripeptide moieties on metal oxide surfaces. The information gained will be important in a number of biomedical related areas from biomedical implants, biosensors, and protein therapeutics as well as in other industries such as maritime, where an understanding of peptide adsorption may enable novel strategies for prevention of biofouling to occur.
These areas are important for a number of reasons, as an ageing population is likely to see an increase in implants. Protein therapeutics may be a solution to the increase in antibiotic resistance in bacteria. In addition, marine fouling is a costly issue which leads to downtime of vessel usage and expensive clean up processes. The work proposed in this travel grant is of a fundamental nature and is likely to contribute to the areas outlined above, informing the choice of materials or design of materials and coatings which enhance or retard protein adsorption. This if developed further, in the longer term would have impact both nationally and internationally. Previous work by the investigators, following an award of a travel grant, led to publications which have been cited in work linked to sensing, cancer therapeutics, novel coatings technology and photocatalyst applications as well as in more fundamental science.
The proposal will also assist in the training of PhD students in state of the art spectroscopic techniques we will use here, and ensure the UK maintains a body of highly-skilled people in complex photoelectron spectroscopy and emerging techniques in photoelectron spectroscopy as well as in the use of synchrotron radiation.
These areas are important for a number of reasons, as an ageing population is likely to see an increase in implants. Protein therapeutics may be a solution to the increase in antibiotic resistance in bacteria. In addition, marine fouling is a costly issue which leads to downtime of vessel usage and expensive clean up processes. The work proposed in this travel grant is of a fundamental nature and is likely to contribute to the areas outlined above, informing the choice of materials or design of materials and coatings which enhance or retard protein adsorption. This if developed further, in the longer term would have impact both nationally and internationally. Previous work by the investigators, following an award of a travel grant, led to publications which have been cited in work linked to sensing, cancer therapeutics, novel coatings technology and photocatalyst applications as well as in more fundamental science.
The proposal will also assist in the training of PhD students in state of the art spectroscopic techniques we will use here, and ensure the UK maintains a body of highly-skilled people in complex photoelectron spectroscopy and emerging techniques in photoelectron spectroscopy as well as in the use of synchrotron radiation.
People |
ORCID iD |
| Andrew THOMAS (Principal Investigator) | |
| Karen Syres (Co-Investigator) |
| Description | The research has shown that there are subtle differences in the way peptides adsorb on metal oxide surfaces with and without the presence of water vapour, and that even post-adsorption wetting with water vapour can lead to changes in the degree of protonation of the peptides. We also found that amino acids undergo subtly different adsorption modes on pre-hydroxylated titanium dioxide surfaces. In almost all cases amino acids are adsorbed via the carboxylic acid group with the amine remaining oriented into the vacuum. We also were able to carry out some measurements of a perovskite material into which peptide gel had been incorporated, which led to a publication. It was found that the peptide gel improves the stability of the lead halide perovskite material, and also gives a small improvement in efficiency when used in a photovoltaic device. Increasing the amount of peptide additive led to a blue shift in the absorption of the perovskite, which we believe is due to the peptide limiting the perovskite growth, resulting in quantum confined nanoparticles. |
| Exploitation Route | We are now looking more into the use of peptides and other polymers to control the growth of lead halide and related halide perovskites and improve the stability of the materials. We are currently preparing a proposal to EPSRC to carry this work forward. The more fundamental work has shown that amino acids and small peptides tend to chemisorb to titanium dioxide through the carboxylic acid group, leaving the amine group free. It is also known that the amine is capable of being incorporated into organo-lead halide perovskites, where they lead to a reduction in defect sites. We believe this may be part of the explanation as to why peptide-perovskite composites result in both higher stability and a modest improvement in power conversion efficiency when used in photovoltaic devices. The new proposal will seek to further understand these [phenomena. More generally, the behaviour following adsorption may also inform pharmaceutical manufacture based on protein therapeutics. Here large amounts of materials is lost du to denaturation of the required peptide/protein in the synthesis process - a problem that appears to be linked to the interaction of the protein with the walls of reaction and transport vessels and tubing. However, it is currently not clear whether this denaturation is caused by the chemical interaction with the vessel walls or due to shear forces in the flowing material. |
| Sectors | Energy Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | Exploring the stability and corrosion mechanisms of oesophageal stents |
| Organisation | The Christie NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We have been developing testing protocols for the corrosion/stability of oesophageal stents, since it has become clear that the long term viability of these devices is not good. This used not to be a problem since the prognosis for patients with advanced oesophageal cancers was poor (~90 days), however improvements in treatments has increased this to 18 months, therefore the metallic stents currently used are corroding in situ and need to be replaced. We are devising test, in collaboration with colleagues at University of Chemistry and Technology, Prague, and will then move on to look at alternative materials/strategies to improve the corrosion resistance, whilst maintaining the desirable properties of the stents. |
| Collaborator Contribution | The Czech group are carrying out similar measurements to us to act as confirmation that the methods for testing the stents are reproducible. They have developed electrochemical testing techniques which we are copying as well, again to check the reproducibility of the data and rigour of the testing protocol. Clinicians from the Christie and Minnova have been supplying samples - both wires from stent manufacturers and full stents, some of which have been explanted |
| Impact | Multidisciplinary involving clinicians, biomaterials and materials characterisation as well as industrial partners. |
| Start Year | 2021 |