Phospholipid Bilayer Properties in pH-Responsive Hemoglobin-Based Oxygen Carriers

Hemoglobin (Hb)-based oxygen carriers (HBOCs) are a potential solution to the growing shortage in the worldwide blood supply. Recent developments in HBOC design have shown that Polyethylene glycol surface-conjugated liposome-encapsulated Hb (PEG-LEH) has shown promising results in mimicking the oxygen uptake and release of human red blood cells. This study aims to use atomistic simulations to investigate the mechanical properties, gas-exchange properties, and pH responsiveness of a novel HBOC which introduces a pH-sensitive molecule (KC1003) to the phospholipid membrane to regulate the uptake and release of oxygen based on pH. Mechanical properties of KC1003 in a phospholipid membrane show that it is a stable phospholipid membrane, with slight structural differences from increasing the concentration of KC1003, where an increased concentration slightly increases lipid disorder. Gas diffusion through the membrane was not limited by the addition of KC1003, and the gas diffusion values were similar to those of red blood cells. Furthermore, the membrane proved to be pH responsive, allowing for the binding and release of 2,3-DPG (2,3-Diphosphoglyceric Acid) at high and low pHs, respectively. These results collectively show that the membrane is mechanically stable at physiological conditions at a molecular scale, allows for proper gas diffusion through the phospholipid membrane, and can act as a pH-sensitive lipid membrane that the concentration of KC1003 can modify. Collectively, these results can be used for tuning of the membrane of an HBOC to mimic the physiological oxygen intake and release of a red blood cell.