The basic physical mechanism responsible for sickling is linear aggregation of deoxygenated molecules of sickle hemoglobin (Hb S) into long fibers within erythrocytes. Although hemoglobin molecules are held together in fibers by relatively weak bonds, bundles of these fibers are strong enough to distort erythrocytes containing them into the well-known sickle-like shapes. A combination of x-ray diffraction studies and electron microscopy has shown that each fiber is made up of six strings of Hb S molecules "in register." The effects of other hemoglobins present in red blood cells along with Hb S on sickling have improved conceptualization of how Hb S molecules fit together. When contact regions have been precisely identified, attempts to devise means of preventing aggregation and sickling can be carried out with a high degree of precision.
Bertles JF. Hemoglobin Interaction and Molecular Basis of Sickling. Arch Intern Med. 1974;133(4):538-543. doi:10.1001/archinte.1974.00320160032004