Impact of Sulphated Hyaluronic Acid on BMP-2 Kinetics and Aggregation

Abstract

Bone morphogenetic protein-2 (BMP-2) stands as a pivotal growth factor within the bone extracellular matrix (ECM), playing a critical role in osteogenesis. Glycosaminoglycans (GAGs), equally vital biomolecules within the ECM, engage in interactions with these growth factors, intricately impacting signal transduction processes. Through a comprehensive array of spectroscopic and rheological methodologies, our study delved into the impact of hyaluronic acid (HA) and its sulfated derivative (SHA) on BMP-2's conformational changes, aggregation dynamics, and the intricate pathways guiding this aggregation process in vitro. The introduction of HA and SHA prompted distinct alterations in the secondary structure of BMP-2: a notable escalation in beta sheet content in the presence of HA and a consequential shift towards unstructured content in the presence of SHA. While both GAGs induced BMP-2 aggregation, their mechanisms diverged significantly. SHA facilitated the swift formation of amorphous aggregates, whereas HA instigated the formation of amyloid fibrils, characterized by a lag phase and sigmoidal kinetics. Higher viscosity, low diffusivity of protein and higher excluded volume In the presence of HA promotes fibrillation having size in micrometer range. Low viscosity, high diffusivity of protein and lesser excluded volume leads to amorphous aggregate of size in nanometer range.