Research

A Closer Look into Polymer/Protein Interaction and the Mechanisms Affecting It.

The adsorption of biomolecules to specific surfaces is important for biomedical areas as diverse as replacement surgery, pathogen screening, biomolecular sensing, and drug delivery. The need to control, prevent and/or sense the adsorption of biomolecules to the surface of materials has fueled synthetic efforts to find better materials capable of doing so. Different avenues can be followed to this end through the use of biological molecules (biocides), surface patterning (super-hydrophobicity) or polymers characterized by high hydration or high exclusion volumes. In our studies we have focused on polymeric functionalization and in particular on the mechanism through which the polymers control the interaction of the surface with proteins.

While PEG has been long known to provide nanocarriers with stealth properties, is toxic under oxidative conditions and produces immunogenic reaction. Studies on poly(phosphoester)s (PPEs) functionalized nanoparticles have demonstrated these nanocarriers to behave very similarly to PEGylated ones showing a lower non-specific cellular uptake after exposure to plasma proteins.

We studied the interaction of proteins with both PEG and members of the polyphosphoesters (PPEs) family (this last part in collaboration with Dr. F. Wurm). We use polymers modified with a hydrophobic tail so that Langmuir monolayers can be formed at the air/water interface to mimic the surface of the nanocarries.

We have investigated how subtle differences in the chemistry of hydrophilic PPEs influence the adsorption of the human blood proteins serum albumin and fibrinogen. Using thermodynamic measurements, surface-specific vibrational spectroscopy, and Brewster angle microscopy, we have investigated protein adsorption, hydration, and steric repulsion properties of the polyphosphoester polymers. Whereas both surface hydration and polymer conformation of the polymers vary substantially as a consequence of the chemical differences in the polymer structure, we have found that the protein repellency ability of these hydrophilic materials appears to be dominated by steric repulsion (1).

However, developing new functional biomaterials requires the ability to simultaneously repel unwanted and guide wanted protein adsorption. Beside confirming that at low concentration PEG allows adsorption of some blood proteins, interestingly we have found that a sweet-spot concentration of PEG exists at which fibrinogen appears to adsorb on the surface in low quantities, but with a net orientation (2). We have also systematically interrogated the factors determining the protein adsorption by comparing the behaviors of different polymeric surfaces, PEG and a PPE and five different natural proteins. Interestingly we observe that, at densities comparable to those used in nanocarrier functionalization, the same proteins are either adsorbed (fibrinogen, human serum albumin, and transferrin) or repelled (immunoglobulin G and lysozyme) by both polymers. However, when adsorption takes place, the specific surface dictates the amount and orientation of each protein (3).

Related Publications:

(1) C. Bernhard, K. N. Bauer, M. Bonn, F. R. Wurm, G. Gonella Interfacial Conformation of Hydrophilic Polyphosphoesters Affects Blood Protein Adsorption - ACS Appl. Mater. Interfaces, 11, 1624–1629 (2019)

(2) C. Bernhard, S. J. Roeters, J. Franz, T. Weidner, M. Bonn , G. Gonella Repelling and Ordering: The Influence of Poly(ethylene glycol) on Protein Adsorption - PCCP 19: 28182-88 (2017)

(3) C. Bernhard, S. J. Roeters, K. N. Bauer, T. Weidner, M. Bonn, F. R. Wurm, G. Gonella* - Both Poly(ethylene glycol) and Poly(methyl ethylene phosphate) Guide Oriented Adsorption of Specific Proteins - Langmuir 35, 14092-14097 (2019)