Abstract
Blood banks around the world store blood components for several weeks ensuring its availability for transfusion medicine. Red blood cells (RBCs) are known to undergo compositional changes during storage, which may impact the cells’ function and eventually the recipients’ health. We extracted the RBC’s cytoplasmic membrane (RBCcm) to study the effect of storage on the membranes’ molecular structure and bending rigidity by a combination of X-ray diffraction (XRD), X-ray diffuse scattering (XDS) and coarse grained Molecular Dynamics (MD) simulations. Blood was stored in commercial blood bags for 2 and 5 weeks, respectively and compared to freshly drawn blood. Using mass spectrometry, we measured an increase of fatty acids together with a slight shift towards shorter tail lengths. We observe an increased fraction (6%) of liquid ordered (lo) domains in the RBCcms with storage time, and an increased lipid packing in these domains, leading to an increased membrane thickness and membrane order. The size of both, lo and liquid disordered (ld) lipid domains was found to decrease with increased storage time by up to 25%. XDS experiments reveal a storage dependent increase in the RBCcm’s bending modulus κ by a factor of 2.8, from 1.9 kBT to 5.3 kBT. MD simulations were conducted in the absence of proteins. The results show that the membrane composition has a small contribution to the increased bending rigidity and suggests additional protein-driven mechanisms.
Highlights
The long term storage of blood components is essential in transfusion medicine
The maximal observed order of lamellar peaks was found to be 4 for a fresh RBC’s cytoplasmic membrane (RBCcm), and up to 6 in case of samples prepared from stored Red blood cells (RBCs). q1 will hereafter refer to the position of the first order lamellar peak
The same changes were observed for the cholesterol rich patches in the Molecular Dynamics (MD) simulations, suggesting that the experimental observations are the effect of higher cholesterol concentrations resulting in a splitting and dispersion of the domains in stored RBCcm
Summary
The long term storage of blood components is essential in transfusion medicine. Blood is first collected from donors and processed into different components, after which they are stored until needed in hospitals around the world. The maximal allowed storage time is 5 to 6 weeks. Blood bank storage of red blood cells alters RBC cytoplasmic membrane order and bending rigidity of General and Medical Sciences, and R01HL146442 (ADA), R01HL149714 (ADA), R01HL148151 (ADA), R21HL150032 (ADA), from the National Heart, Lung, and Blood Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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