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 | We have found that the first monolayer of amino acids deposited from the gas phase in vacuum will bind strongly to titanium dioxide surfaces and that multilayers readily form but that these tend to desorb ay relatively low temperatures. This binding occurs through the acid group of the amino acid, rather than the amine in agreement with calculations and the study of related molecules. We have also found that the amino acids stand upright on the surface of the titanium dioxide surface and appear relatively stable on the surface. We are now moving to look at how these molecules attach in the presence of water. We have also expanded the project slightly to investigate the use of peptide gels to improve the stability of the metal halide perovskite materials used in photovoltaic cells. We find that these peptide gels impart some improvement in stability, but unfortunately negatively affect the quality of the perovskite grains, and the efficiency of devices. We are now looking at methods to improve the grain structure since this should lead to further improvements in stability, and also efficiency. This is interesting since if bio-molecules can be used for these kinds of applications it will potentially reduce our reliance of petrochemicals for the synthesis of polymers. |
| Exploitation Route | We are now looking to determine what happens when the amino acids are deposited from water or onto a hydroxylated titanium dioxide surface. This is important because clearly in real biological systems water will be present. We have recently developed a method to deposit the molecules from solution in an inert atmosphere onto atomically clean titanium dioxide crystals. In addition, we will go on to look at the effect of pH on the solution in which the amino acids are presented, and whether this affects the uptake of the amino acid. |
| Sectors | Chemicals,Energy,Healthcare |
| 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 |