Role of Salts and Surfaces on ECM Constituents in Biological Media

Abstract

For Cell based therapies having chemically defined surfaces with chemically defined media offer an advantage with respect to growing these cells. Typical constituents of the media are a number of different inorganic salts and ECM mimectics that can enable cell adhesion. It is critical to understand the interactions between the ECM mimectics, salts and the surfaces for effective design of such media and the surfaces. In this work, we probe the conformation of a specific ECM mimectic (ProNectin F) in solution with a change of concentration of commonly used monovalent (KCl, NaCl) and divalent (CaCl2) salts. Using Molecular Dynamics we find there is an effect of ion-induced conformation change on the active RGD site of Pronectin F. This conformational change is stronger in a CaCl2 solution compared to KCl and the mixed salt solutions show a larger RGD active site angle fluctuation. We also study the interaction between the different conformations of Pronectin F with different salts and integrin using both MD and docking techniques. We find that the type of cation also has a significant role in altering the RGD binding site on the integrin. Then we look into the role of the surface adhesion with water and Pronectin F. Hydrophobic residues play an important role in how this mimectics adheres to the surface. This adhesion process decreases hydrogen bonding to allow for a structural change that minimizes the interaction between the hydrophobic residue and water to increase its interactions with the surface.