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Human erythrocytes (RBCs) have a lifespan of approximately 120 days, during which they accumulate oxidative damage and eventually become removed from the circulation by the immune system. The clustering of membrane protein band 3 is an essential process in the clearance of damaged and aged RBCs, however the detailed molecular mechanisms of cluster formation remain poorly understood. In this study, we developed a computational model that reproduces the biochemical behavior in RBCs during oxidative treatment, to quantitatively understand the spatiotemporal dynamics and regulatory mechanisms of band 3 clustering. We observed that cluster size and reversibility reflect cellular oxidative capacity, and that strong attractive forces between phosphorylated band 3 greatly contribute to cluster formation. Simulation analyses of clustering with incorporation of a mesh-like structure, implied that compartmentalization of band 3 by spectrin at initial state plays a role in inhibiting cluster formation, and suggested that clustering significantly disrupts the reassembly of the spectrin cytoskeletal network after oxidation. Taken together, our results provide predictive insights on the detailed reaction dynamics of band 3 clustering, its role in RBC senescence, and how it is regulated in vivo.
E Shimo H, Nishino T, Arjunan S, Takahashi K, Tomita M. gComputer simulations of oxidative stress induced membrane protein clustering in human erythrocytesh, Kaketsuken The 8th Aso International Meeting, Aso, Japan