(681f) Paired Simulations and Experimental Investigations into the Calcium-Dependent Bioactivity of Albumin

In the United States, over 130,000 surgical procedures each year require the use of bone grafting material. Despite the advancement in surgical technique as well as graft material, ~30% grafts result in failure. Therefore, a significant opportunity exists for novel biomaterials to address this clinical need. Recent studies have implicated that albumin is important for improving biomaterial integration with bone tissue. In contrast, there are studies demonstrating albumin blocks cell adhesion to biomaterials, which leads to limited bone healing capabilities. These studies indicate that there is a bioactive conformation of albumin which facilitates bone repair through osteoblast cell adhesion.

Experimentally, it was found that bovine albumin coated substrates facilitate MC3T3-E1 osteoblast-like cell adhesion only after they have been exposed to calcium containing buffer. The cell adhesion levels further increase with increasing calcium concentrations. These experimental results are explained through a series of atomistic and coarse-grained molecular dynamics (MD) simulations to understand the Ca²⁺ ion dependent conformational changes that occur in the three-dimensional structure of albumin. Atomistic MD simulations in the presence and absence of docked Ca²⁺ ions were first performed to identify the local conformational changes. Coarse-grained MD simulations were then performed to investigate large scale conformational changes and the effect of varying Ca²⁺ ion concentrations in the bulk of the simulation box on the albumin conformation. In our preliminary analysis, we were able to identify the regions on the albumin structure undergoing conformational changes. Moreover, we observed that 0.5 M Ca²⁺ ion concentration had a significantly larger stabilizing effect on albumin conformation than 0.1 M Ca²⁺ ion concentration. These preliminary simulation results are in agreement with the experiments, where higher Ca²⁺ ion concentrations were found to be stabilizing the albumin conformation and also provide evidence of Ca²⁺ ion concentration dependent conformational changes.