Williams Dillon C, Szafraniec Hannah M, Wood David K
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Biophys Rev (Melville). 2025 Mar 20;6(1):011309. doi: 10.1063/5.0238698. eCollection 2025 Mar.
Sickle cell disease is a hereditary disorder in which the pathophysiology is driven by the aggregation of a mutant (sickle) hemoglobin (HbS). The self-assembly of deoxygenated sickle hemoglobin molecules into ordered fiber structures has consequences extending to the cellular and rheological levels, stiffening red blood cells and inducing pathological flow behavior. This review explores the current understanding of the molecular processes involved in the polymerization of hemoglobin in sickle cell disease and how the molecular phase transition creates quantifiable changes at the cellular and rheological scale, as well as, identifying knowledge gaps in the field that would improve our understanding of the disease and further improve treatment and management of the disease.
镰状细胞病是一种遗传性疾病，其病理生理学由突变型（镰状）血红蛋白（HbS）的聚集驱动。脱氧镰状血红蛋白分子自组装成有序的纤维结构，其影响延伸至细胞和流变学水平，使红细胞变硬并引发病理性流动行为。本综述探讨了目前对镰状细胞病中血红蛋白聚合所涉及分子过程的理解，以及分子相变如何在细胞和流变学尺度上产生可量化的变化，同时还确定了该领域的知识空白，这些空白将有助于增进我们对该疾病的理解，并进一步改善疾病的治疗和管理。
