The Whats, The Hows and The Whys of Protein Adsorption

Proteins can bind to a variety of surfaces that we use in everyday life, including most plastics, glass, metals, and even in the body and as medicines. This phenomenon has some desirable applications for example, immunological testing; however, it does have unintended consequences such as loss of expensive protein medicines and impaired function of medical devices. This article provides a brief explanation of what this phenomenon is, how it occurs and why scientists are trying to decrease the risk of adsorption and minimize the consequences.

Figure 1: Relevant examples of everyday applications that are influenced by protein adsorption. Created with BioRender.com.

Proteins are large complex molecules that have both water-liking (hydrophilic) and water-hating (hydrophobic) groups. In addition, they carry positive and negative charges in their structures. It is these groups that interact and quite often, irreversibly with our everyday materials. Protein adsorption to a surface is a very common but exceptionally complicated phenomenon and is of much interest across various disciplines some of which include drug delivery, medical device, biotechnology, cell biology, and analytical science.

 

Considering how commonplace this phenomenon is, the importance of understanding the factors that influence this process and the implications in the context in the manufacture, design, and drug delivery in medical products and devices is extremely important. Additionally, understanding the protein adsorption behavior and mechanisms at solid surfaces has been crucial to developing effective solutions. We need solutions because protein adsorption is problematic in the pharmaceutical and medical device industry for two very important reasons:

1.  Protein adsorption can lead to a change in the shape and functionality leading to increased manufacturing’s.

2.  Protein adsorption can impair the functionality of implantable medical devices.

Figure 2: Illustration of Protein structure. Created with BioRender.com.

Finding these solutions and solving the protein adsorption paradox has been driven by the need to understand the adsorption–desorption phenomena that occurs on material surfaces. Over the last 50 years, research into protein-surface interactions and the protein environment has determined several factors that influence the adsorption process some of which include protein concentration, protein size, and surface properties. Nevertheless, despite the level of knowledge in the field, a molecular-level understanding of all aspects of protein adsorption is still incomplete, particularly with observed phenomena such as protein orientation, influence of other molecules, and aggregation on the material surface. Protein adsorption is not a process that is the same for every protein, in fact, it varies for each type of protein and attempting to understand how this manifests for each one is a slow process.

Figure 3: Illustration of proteins in solution adsorbed to the material surface of an iv bag and a syringe. Created with BioRender.com.

To date, by understanding protein adsorption scientists have been able to devise ways to harness this phenomenon more effectively to create smarter biosensors and purify medicines more effectively. It has also inspired important strategies to control/minimize adsorption where undesirable. Some recent developments in the areas of excipients and polymer brushers have proved successful in hindering protein adsorption. Several ways scientists have already tackled the adsorption challenge are outlined below!

1. Bovine Serum Albumin (BSA): BSA can irreversibly bind to the material surface and because it is such a large protein, it can prevent small molecule drugs from binding to the material surface. BSA does not interfere with any enzymatic reactions and can even stabilize other proteins.
2. Excipients: Using excipients such as phosphates, polysorbate or sugars at low concentrations is an inexpensive and easy-to-use method to limit adsorption.
3. Surface Modification: Polyethylene glycol, polyacrylic acid and self-assembled monolayers can be used to coat materials and reduce the amount of adsorption sites on the surface by repelling proteins back into solution.
4. Salt: Increasing the salt concentration is a technique that can also be used to prevent adsorption. This technique is delicate and if made too concentrated, there is a chance of disruption to the protein structure.
5. Environment: It is important to use the optimal buffer for the protein and that the buffer is made to a suitable pH and strength. It is also important to conduct the experiment at a suitable temperature relevant to the individual protein.

Figure 4: Illustration of protective layer on material surface which prevents protein adsorption to the surface. Created with BioRender.com.

It is important to remain hopeful for the future and that as research into adsorption progresses, better medical device implants and biologic drugs for patients become available. There are many researchers around the world working to reveal the obscurities surrounding the phenomena of protein adsorption and as public knowledge of this research area increases, improved funding and knowledge will become available to help solve the puzzle.