Protein misfolding and aggregation can lead to several disease states and can significantly impact the biopharmaceutical processes of biological therapeutics. While shear-stress and surface adsorption are known to contribute to protein aggregation, these phenomena have been underestimated so far, highlighting the importance of developing approaches and tools to study surface aggregation and the effects of shear. The objective of this review is to highlight the impact of shear and surfaces on protein aggregation; both experimentally and computationally. Inorganic materials and biologically relevant surfaces are discussed to evaluate different surfaces influencing the aggregation pathways of polypeptide chains, along with their internal (mutations, structures, disulfide-bridges, dynamics, net charges) and external factors (pH, ionic strengths and specific ion effects, temperatures, metal ions). Advanced experimental methods offer a realistic framework for investigating protein aggregation under physiologically relevant conditions. However, there is currently no comprehensive computational framework to explain and to address these shear-dependent phenomena due to the large variety of proteins and pathways involved. In summary, the present review offers an exhaustive appreciation of surface- and shear-induced protein aggregation, which will provide impactful strategies for treating diseases and improving biopharmaceutical processes. • Shear stress can affect protein structure, potentially inducing aggregation and/or denaturation. • Physicochemical surface properties dictate protein-surface interactions, which affect protein structure and solubility. • Effective surface characterization techniques probe protein structures assembled on specific surface types. • Physiological shear emulating settings predict mechanical effects during real-time biological therapeutics. • Experimental and computational molecular/fluid dynamics are models to support and propose unrecognized relationships.
Jegamohan et al. (Fri,) studied this question.