In situ synchrotron imaging of human serum proteins interactions, molecular docking and inflammatory biomarkers of hemocompatible synthesized zwitterionic polymer coated-polyvinylidene fluoride (PVDF) dialysis membranes

Abstract

Hemodialysis (HD) treatment leads to biochemical cascades due to protein adsorption and interactions, resulting in life-threatening side effects in many patients. Hemodialysis polyvinylidene fluoride (PVDF) membranes, independent of their structures and geometries, record impeded permeation performance due to their fouling-prone hydrophobic nature. In the present study, a clinical grade PVDF membrane was surface-modified with a new zwitterionic polymer (ZW) synthesized from a ring-opening polymerization between poly (maleic anhydride-alt-1-decene),3-(dimethylamino)-1-propylamine derivative and 1,3-propanesultone. Both coated and untreated PVDF membranes were characterized using appropriate surface analytical techniques before investigating the extent of serum protein fouling and interaction on each membrane surface using Synchrotron Radiation Micro-Computed Tomography (SR-µCT). The adsorption of fibrinogen bounded nanoparticles and their subsequent fouling on the membrane were only intensified within the topmost and mid-sectioned layer for the bare membrane. Surface imaging did not reveal significant presence of adhering protein on the ZW coated membrane surfaces; the results collected from scanning electron microscopy (SEM) and SR-µCT imaging are consistent and in agreement. Reduced episodes of multiprotein could contribute to limited tendencies for biological activations on coated membrane compared to its bare counterpart. This suggests that the bare membrane was a potent complement, coagulation, and inflammation activator; hence, it was bio-incompatible with the uremic blood sample upon contact. This ZW coated membrane also expressed less inflammatory biomarker releases upon incubation in uremic blood samples of chronic kidney disease (CKD) patients undergoing HD therapy. This clinical trial was conducted with a technique consistent with Luminex assays for eight biomarkers. Experimental investigations were also corroborated with in-depth molecular modeling docking in the quest to probe the interactions at active sites of three protein models. Docking of most potent structures into the human serum albumin active sites exhibited two important interactions: a hydrophobic interaction of protein backbones with PVDF model accompanied by polar interactions between CF groups and Arg257. This interaction related to the highest electronegativity from the fluorine atom. The presence of the novel ZW on PVDF significantly reduced protein adhesion due to polymer's positive/negative charged units.