Molecular Mechanism of Vitronectin Structural Evolution on Distinct Surface Chemistries: The Mediation for Cell Adhesion

Surface chemistry of biomaterials plays a fundamental role in the adsorption of vitronectin (Vn), a crucial mediator for cell adhesion. However, the detailed structural information and dynamics mechanism of Vn adsorption to distinct surface chemistries relevant to its biological effect remains elusive. Herein, the conformation and orientation evolution during Vn adsorption to self-assembled monolayers terminating with -COOH, -NH₂, -CH₃ and -OH were investigated. To unravel the interplay between cell binding and surface charge and wettability, the N-terminal somatomedin-B domain housing the cell-binding motif of Vn was recruited in molecular dynamics simulations optimized with orientation initialization by Monte Carlo method. Experimental evidences including protein adsorption, cell adhesion and integrin gene expressions were thoroughly investigated. The adsorption of Vn on different surface chemistries showed very complex profiles. Cell adhesion was enabled on all the Vn-adsorbed surfaces but with distinct mechanisms relating to the adsorption quantity and orientation of Vn. The negatively charged surface (COOH) and the hydrophobic surface (CH₃) adsorbed Vn with higher quantity and density. However, advantageous orientations with unrestrained and active cell-binding RGD loops were only obtained on the charged surfaces (COOH and NH₂) instead of the non-charged (CH₃ and OH). Specifically, the negatively charged surface stretched and stood up the Vn into a higher density, whereas the hydrophobic surface squashed the Vn into higher density multilayer by tracking adsorption but with the RGD loops restrained. These findings may have a broad implication on the understanding of Vn functionality as well as the designing of advanced biomaterials.