L-Serine Grafted PSF Affinity Membrane And Performance For Endotoxin Removal

Endotoxin, the lipopolysaccharide (LPS) component of the outer cell wall of Gram-negative bacteria, often leads to a strong biological reaction through activation of immune system after entering the human blood system. It is considered to be the primary trigger of sepsis, the common clinical problem in the intensive care units (ICUs) with continuously increasing hospitalization rate and extremely high general mortality. Affinity adsorption method is a fairly acceptable way of eliminating the circulating endotoxin in vitro to help alleviate the symptoms of this disease, which has remarkable sense for sepsis treatment.In this work, commercial PSF hollow fiber hemodialysis membranes were chosen as the matrix. Considering the poor organic solvent-tolerance of PSF material, the membrane surface was rationally modified through a chemical modification route at normal temperature to maintain the characteristic of the polymer matix. Firstly active group-CH2CI was introduced onto the PSF membrane surface basing on the Friedel-Crafts reaction, then ethylenediamine (EDA) was fixed afterwards as the space arm. The resulting membrane was activated with glutaraldehyde and finally grafted with L-serine (Ser) ligand. The Ser density on the membrane could be controlled by adjusting the chloromethylation reaction time at the beginning. The proper chloromethylation time was found to be60min and the corresponding ligand density was2.04μmol/cm2. ATR-FTIR spectra and XPS results confirmed the change of the surface chemistry. The static water contact angle test showed that PSF-Ser membrane became much more hydrophilic after the modification.The endotoxin adsorption capacity of membrane in deionized water, phosphate buffer and BSA solution all increased after L-Ser immobilization. The adsorption behavior was affected by the pH value, ionic strength, endotoxin level and protein concentration of the solution. The endotoxin adsorption capability was1.656EU/cm2in the phosphate buffer which exactly fit the operating conditions of blood treating (pH=7.0,0.15M). Comparing to the PVDF-Ser affinity membrane previously prepared in the lab, PSF-Ser membrane showed an increased endotoxin capacity and a similar BSA adsorption performance.Molecular dynamics simulation model of Lipid A, the active and conserved part of endotoxin, was established in the CHARMM field to find the interaction mechanism between ligands and endotoxin from molecular level. Initial configuration showed that a stable Lipid A lamellar bilayer was formed in water and the sickness of the bilayer was calculated to be4.65nm/4.98nm. The structure and sickness were both the same as the literatures, which confirmed that the parameters of the field were credible. Besides, there were also atomistic descriptions about the bilayer structures of Lipid A.These results showed that the prepared PSF-Ser affinity hollow fiber was able to adsorb endotoxin selectively from aqueous solutions and protein solutions. So this endotoxin adsorption membrane might be a kind of potential promising blood purification method for sepsis treatment. Meanwhile, the field model of Lipid A was useful for further molecular dynamics research, which contributed to lay a foundation for mechanism discussion of endotoxin and ligand interactions.