ABSTRACT

A common approach in modern cell biology and medicine has been to elucidate the various processes and attributes of the living organism through an analysis of the behavior of its most basic constituents. Consequently, much of what is now known about the macromolecular assemblies responsible for cellular function and integrity has arisen from exhaustive in vitro characterization of the individual components that contribute to their structure. This approach, although limited to the test tube, has provided much of the guidance for the construction of conceptual frameworks from which the rules governing cell function and organization can be inferred. Such strategies have found great utility in the elucidation of the factors responsible for the strength and mechanical stability of the human erythrocyte membrane, properties it derives from an anastomosing network of proteins attached to its cytoplasmic surface. Referred to as the “membrane skeleton,” this macromolecular assembly has been the focus of two decades of intense investigation. The cumulative result of these efforts has been the construction of a conceptual model of the membrane skeleton consistent with both the biomedical properties of its individual protein components and the 2physiological characteristics of its macromolecular form. The operational impact of this construct has been as a schematic paradigm for detailed discussion of membrane skeletal structure in normal and abnormal erythrocytes and for initial studies of the more complex membranes in nonerythroid cells.