Simulation-based assessment of zwitterionic pendant group variations on the hemocompatibility of polyethersulfone membranes

Abstract

In the realm of hemodialysis, Polyethersulfone (PES) membranes dominate due to their exceptional stability and mechanical properties, capturing 93% of the market. Despite their widespread usage, the hydrophobic nature of PES introduces complications in hemodialysis, potentially leading to severe adverse reactions in patients with end-stage renal disease (ESRD) through protein fouling. Addressing this issue, our study focused on enhancing hemocompatibility by modifying PES surfaces with zwitterionic materials, known for their hydrophilicity and biological membrane compatibility. We investigated the functionalization of PES membranes utilizing various zwitterions in different ratios. Utilizing molecular docking, we examined the interactions of three zwitterionic ligands-carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl) phosphorylcholine (MPC)-with human serum proteins. Our analysis revealed that a 1:1 ratio of phosphobetaine and sulfobetaine exhibits the lowest affinity energy towards serum proteins, denoting an optimal hemocompatibility without the limitations associated with increased zwitterion ratios. This pivotal finding offers a new pathway for developing more efficient and safer hemodialysis membranes, promising improved care for ESRD patients.

Supplementary information: The online version contains supplementary material available at 10.1186/s42252-024-00062-6.

Keywords: Affinity energy; Carboxybetaine; Hemocompatibility; Molecular docking; Pendant groups; Phosphobetaine; Protein-ligand interaction; Sulfobetaine.

Fig. 1

Chemical structures and stick view (with energy minimization) of polyethersulfone (PES) and zwitterion chains (PB, SB & CB)

Fig. 2

(a) 2D interaction diagrams, and (b) Electrostatic interaction profiles for the docking of CB with HSA, FB and TR

Fig. 3

(a) 2D interaction diagrams, and (b) Electrostatic interaction profiles for the docking of SB with HSA, FB and TR

Fig. 4

(a) 2D interaction diagrams, and (b) Electrostatic interaction profiles for the docking of PB with HSA, FB and TR

Fig. 5

(a) 2D interaction diagrams, and (b) electrostatic maps of interactions of docking CB-PES with HSA, FB and TR

Fig. 6

(a) 2D interaction diagrams, and (b) electrostatic maps of interactions of docking SB-PES with HSA, FB and TR

Fig. 7

(a) 2D interaction diagrams, and (b) Electrostatic interaction profiles for the docking of PB-PES with HSA, FB and TR

Fig. 8

(a) 2D interaction diagrams, and (b) Electrostatic interaction profiles for the docking of CB-PB-PES (1 to 1 ratio) with HSA, FB and TR

Fig. 9

(a) 2D interaction diagrams, and (b) Electrostatic interaction profiles for the docking of CB-SB-PES (1 to1 ratio) with HSA, FB and TR

Fig. 10

(a) 2D interaction diagrams, and (b) Binding energy outcomes and receptor interactions of SB-PB-PES (1:1 ratio) with HSA, FB and TR