Speaker: Prof. Christine Payne
Subject: Material-cell interactions
Location: Delft University of Technology
Author: Romano van Genderen
This talk by professor Payne was divided into two parts, the first about nanoparticle-cell interactions and the other one about the synthesis of conducting polymers by cells.
She started by explaining the use of nanoparticles in current research. These particles are often used for tracking and sensing molecules in biological research. They also have a hypothetical use as delivery agents for drugs and nucleic acids into cells. But if they want to use this second application of nanoparticles in humans instead of in controlled testing environments, they first must investigate a specific point, the interaction between serum (blood without any living cells or coagulation factors present) and these particles; this is the case because the drugs must obviously be injected into the blood stream. This is why they investigated the nanoparticles in FBS (foetal bovine serum) and MEM (minimal essential medium). They observed the presence of a so-called corona, which is a coating of proteins on the surface of the nanoparticle. This corona consists mostly of albumin, the most common protein in the blood which plays a very important role in regulating the osmotic pressure of the blood. This detection was done using epi-fluorescence.
Afterwards they added cells to the mixture and discovered that cationic nanoparticles only bind the cells if free protein is present. But if the nanoparticle is anionic, it only binds when protein bound to the nanoparticles is present. This is specific for the protein albumin. This shows that the protein albumin changes shape in the presence of a cationic or an anionic nanoparticle. These two different structures of albumin have different receptors on the cell surface. To be sure this did not depend on the material of the nanoparticles (polystyrene), they repeated the experiment using quantum dots, and the same result occurred.
To investigate if the albumin really does have two different structures, they used circular dichroism (CD) spectroscopy, where circularly polarised light is used to detect differences in the secondary structure of proteins. This showed that the protein keeps the same shape when bound to the anionic nanoparticle, but that the cationic particle causes it to change shape to a form with far less α-helices.
Afterwards she mentioned another kind of nanoparticle, which is not really a real nanoparticle but a nanoparticle aggregate. This is titanium dioxide (TiO2), also known as an additive in food called E171. Because this molecule also enters the blood stream, it must be known how it reacts to albumin and if it changes its structure to make sure it is not harmful. In small doses it is not, but it has been shown that it can change peroxiredoxin genes which influence the breakdown of hydrogen peroxide in the cell.
The second and shorter part of the talk was about the synthesis of conducting polymers by cells. This is the polymerisation of EDOT and PSS to a conducting compound called PEDOT:PSS. This was usually done using the peroxidase proteins of plants as catalysts, but now they can also do it using animal peroxidase. But the peculiar thing here is that the protein does not even need to be active, because even after boiling the protein, the reaction still occurred. They thought that perhaps the iron inside the heme bound to the peroxidase plays a role, so they used an iron importer molecule; this did also cause the reaction to occur. So only iron must be present.
Image 1: The structure of a peroxidase, namely peroxidase from a P. chrysosporium. Note the heme molecule bound in the middle and especially the iron-II bound (gray atom surrounded by 4 blue atoms) http://pfam.xfam.org/structure/getimage?id=2gj1
But the kind of protein used does actually matter in the form of the polymer used. Using a protein that binds heme causes a so-called bipolaron state, which leads to a very high conductivity of around 20 S/cm. But a protein that binds bare iron-II causes a polaron state, which has a far lower conductivity. This conductivity is still low compared to metal wires, but it definitely makes up for this lower conductivity in flexibility.
This talk was really fascinating because it showed how theoretical physics eventually got a practical use, the nanoparticles for drug delivery and the wires for in electronics. Especially the conducting polymers were completely new for me; I never expected that cells could make such practical structures.