Designer Materials to Control Competitive Protein Binding

A problem presented at the UK MMSG Keele 2012.

Presented by:
Dr Paul Roach (Institute for Science and Technology in Medicine, Keele University)
JB Butcher, CJ Chapman, GS Francisco, O Kuforiji, P Roach, PA Roberts, JP Ward, RJ Whittaker

Problem Description

Biological activity at a material’s interface is dictated by the ability of the surface to support protein adhesion. This is important in a variety of situations, from anti-fouling properties required in marine technology manufacture, solar cell technology and implantable or point-of-care biotechnology, to the other extreme where bio-fouling is required for cell attachment and tissue build-up.

One of our research directions is to examine how a multi-protein system organises itself to form a mixed protein population at a surface. The composition of a protein layer adsorbing from a mixed populations of proteins is dependent upon the concentration of each species and the affinity between each adsorbate and the surface. This interaction can be altered by changing the characteristics presented at the surface. Surface chemistry is well known to sway protein adsorption characteristics dependant largely upon the hydrophobic and charge compensating interaction between an adsorbing molecule and the surface, whilst surface curvature on the same length-scale as a protein molecule has been shown to alter the structure of the molecule upon adsorption, and therefore alter the interaction affinity.

The study group participants are asked to mathematically model this problem at 2 levels.

  1. To model the adsorbing protein layer at the macro-scale. Such a model can be used to highlight how surface and protein solution properties change the composition of a protein/multiple protein layer.
  2. To model the interaction of a single protein molecule at the nano-scale. This is a more complex problem involving protein-surface or protein-protein-surface interaction mechanisms.

The models will allow us to predict how designer surfaces presenting nano-scale features of varying chemical functionality can be used to steer protein layer composition such that they are cell non-/adherent.

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Study Group Report

We have successfully developed two models able to investigate the adsorption characteristics of proteins having different solution concentrations, surface affinities, sizes and therefore binding areas and also having them compete for surface adsorption sites. Using these models we have shown that the dynamic nature of protein adsorption can be accounted for in this way, restricting models to incorporate only these conditions affords simulations not unlike those found experimentally. Adsorption profiles as well as steady-state surface protein concentrations can be estimated from such simulations, using experimentally derived dimensions and affinity constants to further evaluate protein accumulation at surfaces.

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