Critical Influences of Plasma pH on Human Protein Properties for Modeling Considerations: Size, Charge, Conformation, Hydrophobicity, and Denaturation

Abstract

The fouling of biomaterials (e.g., membranes) by plasma proteins has always garnered attention because it renders biomedical devices ineffective and can jeopardize the patient’s well-being. Modeling the fouling process sheds light on its mechanisms and helps improve the biocompatibility of biomaterials. Assuming proteins to be hard spheres with uniform surface properties reduces the modeling complexity, but it seriously deviates from the accurate, real perspective. One reason for the inaccuracy is that proteins’ properties tend to change as environmental factors such as pH and ionic strength are varied. This study critically reviews the pH-induced changes in protein properties, namely size, charge, conformity, hydrophobicity, and denaturation. Though these properties may be interrelated, they are addressed individually to allow for a thorough discussion. The study illustrates the necessity of incorporating the protein property changes resulting from pH alteration to better explain and model the fouling process. The discussion is focused on human serum albumin and fibrinogen. Human serum albumin is the most abundant plasma protein, while fibrinogen plays a major role in blood clotting and triggering of the thrombogenic response.