Polymorphism of sickle cell hemoglobin aggregates: structural basis for limited radial growth

Fibers composed of molecules of deoxygenated sickle cell hemoglobin are the basic cause of pathology in sickle cell disease. The hemoglobin molecules in these fibers are arranged in double strands that twist around one another with a long axial repeat. These fibrous aggregates exhibit a pattern of polymorphism in which the ratio of their helical pitch to their radius is approximately constant. The observed ratio agrees with an estimate of its value calculated from the geometric properties of helical assemblies and the degree of distortion that a protein-protein interface can undergo. This agreement indicates that the radius of an aggregate is limited by the maximum possible stretching of double strands. The geometric properties limiting the radial extent of sickle hemoglobin fibers are fundamental to all cables of protein filaments and could contribute to the control of diameter in other biological fibers such as collagen or fibrin.