Ligand-linked phase changes in a biological system: applications to sickle cell hemoglobin.

Polyphasic linkage is a close analog of the allosteric and polysteric linkages shown by many biological macromolecules. Like them, it gives rise to both homotropic and heterotropic effects. It is governed by a group of linkage potentials applicable to each separate phase and also, subject to certain conditions, by a group of lower order applicable to the whole system, globally. A good example of polyphasic linkage is provided by sickle cell hemoglobin which, under suitable conditions and subject to control by oxygen, precipitates out of solution to form what appear to be microtubules. This is but one instance of the way in which macromolecular assembly and the formation of subcellular structures generally can be regulated by various small molecules acting as ligands.