A Comparative Assessment of Human Serum Proteins Interactions with Hemodialysis Clinical Membranes using Molecular Dynamics Simulation

Abstract

End stage renal disease (ESRD) affects ≈10% of the world's population. Hemodialysis (HD) is a life-sustaining extracorporeal blood purifying treatment for ESRD patients. Despite the advances in technology, the hemoincompatibility of the dialyzers leads to a high morbidity and mortality rate. Decreasing interactions between polymers and blood constituents will result in controlled binding of human serum proteins to the surface and consequently enhanced biocompatibility. This study aims to assess the interaction energy between common hemodialysis polymer structures and human serum proteins using molecular dynamics simulation to offer a framework for understanding the dominant interactions as a reference for material development. Molecular dynamics and molecular docking simulations are conducted for calculating polymerprotein binding energies. Common serum proteins are selected for protein models. Poly aryl ether sulfone (PAES) with and without polyvinyl pyrrolidone (PVP), polyvinylidene fluoride (PVDF), cellulose triacetate (CTA), polyacrylonitrile (PAN), and polymethyl methacrylate (PMMA) membrane structures are chosen as the different classes of dialyzers. The van der Waals interactions between polymers and proteins dominate the binding energies sequence. Molecular docking results of the affinity between protein receptors-ligands are aligned with the MD binding interaction.

Aminolysis-Based Zwitterionic Immobilization on Polyethersulfone Membranes for Enhanced Hemocompatibility: Experimental, Computational, and Ex Vivo Investigations

“…In vitro clinical assessments reflected better immune system response and lower inflammatory biomarker secretion after the addition of zwitterionic structure [40]. Our research group has focused on interaction profiles and modification of polymeric membranes experimentally and computationally [1, 9,11,[37][38][39][40]. We have also reviewed the most recent theories in the field of hemocompatibility improvement [12].…”

“…PES has a higher clearance efficiency compared to PSF [ 7 ]. Nevertheless, PES membranes still contain shortcomings, including limited hemocompatibility [ 1 , 8 , 9 ], which triggers blood activation cascades, as the rate of morbidity and mortality in ESRD patients is still unacceptably high [ 3 , 10 , 11 , 12 ]. Reactions between blood proteins and the incompatible PES structures trigger the functional sites of the proteins.…”

Electrostatic Repulsive Features of Free-Standing Titanium Dioxide Nanotube-Based Membranes in Biofiltration Applications

“…Therefore, scientists are still researching to enhance the biocompatibility and antibacterial behavior of polymeric hemodialysis membranes. 6,7 Synchronously, less allergic, less cloggable, and more biocompatible ceramic membranes and clay mixtures have also been investigated as alternative materials for polymer and polymer-based composites. 8,9 With increasing progress in the development of nanomaterials and nanotechnology, the volume and weight of the blood filtration systems are drastically reduced, and the patient's life quality has increased after the emergence of artificial kidneys (AKs).…”

“…During the last 15 years, the number of patients struggling with chronic kidney disease (CKD) has increased, although most reasons of CKD, such as genetics and smoking habits, are well known and shared with the community. − Unlike acute kidney disease, a definitive treatment has not been found yet for CKD, considering that conventional devices reduce a patient’s daily activities and comfort. , Although high-flux hemodialysis machines are extremely efficient in shortening a patient’s hospital retention time by assisting in increasing the reduced glomerular filtration rate (GFR) due to CKD, mechanically stable polymeric membranes inside the dialyzers may cause allergic reactions during operation. Therefore, scientists are still researching to enhance the biocompatibility and antibacterial behavior of polymeric hemodialysis membranes. , Synchronously, less allergic, less cloggable, and more biocompatible ceramic membranes and clay mixtures have also been investigated as alternative materials for polymer and polymer-based composites. , …”

“…Normalized fluxes were calculated as the ratio of instant permeate flux (J) and initializing permeate flux (J 0 ) as described in eq 6 given below. 70,71 = J J normalized flux 0 (6) In this study, Coulomb's law was adopted to present the electrostatic interaction between the two same charges (Q 1 and Q 2 ), where k e is Coulomb's constant and r is the distance between charges, as given in eq 7. 72 =…”