Surface nanotopography mediated albumin adsorption, unfolding and modulation of early innate immune responses

Surface roughness plays an important role in regulating protein adsorption to biomaterial surfaces and modulating the subsequent inflammatory response. In this study, we examined the role of surface nanotopography on albumin adsorption, unfolding and subsequent immune responses. To achieve the objectives of the study, we create model surfaces of hill-like nanoprotrusions by covalently immobilizing gold nanoparticles (AuNPs) of predetermined sizes (16, 38, and 68 nm) on a functional plasma polymer layer. The amount of adsorbed albumin increased with the increase in surface area caused by greater surface nanotopography scales. Circular dichroism spectroscopy was used to evaluate albumin conformational changes and pointed to loss of α-helical structure on all model surfaces with the greatest conformational changes found on the smooth surface and the surface with largest nanotopography features. Studies with differentiated THP-1 cells (dTHP-1) demonstrated that immune cells interacted with surface adsorbed albumin via their scavenger receptors, which could bind to exposed peptide sequences caused by surface induced unfolding of the albumin. Pre-adsorption of albumin resulted in an overall decrease in the level of expression of pro-inflammatory cytokines from dTHP-1 cells. On the other hand, pre-adsorption of albumin led in an increase in the production of anti-inflammatory markers, which suggests a switch to the M2 pro-healing phenotype. The knowledge obtained from this study could instruct the design of healthcare materials where the generation of targeted surface nanotopography and pre-adsorption of albumin may enhance the biomaterial biocompatibility and lead to faster wound healing.