title: Curling and local shape changes of red blood cell membranes driven by cytoskeletal reorganization.
abstract: Human red blood cells (RBCs) lack the actin-myosin-microtubule cytoskeleton that is responsible for shape changes in other cells. Nevertheless, they can display highly dynamic local deformations in response to external perturbations, such as those that occur during the process of apical alignment preceding merozoite invasion in malaria. Moreover, after lysis in divalent cation-free media, the isolated membranes of ruptured ghosts show spontaneous inside-out curling motions at the free edges of the lytic hole, leading to inside-out vesiculation. The molecular mechanisms that drive these rapid shape changes are unknown. Here, we propose a molecular model in which the spectrin filaments of the RBC cortical cytoskeleton control the sign and dynamics of membrane curvature depending on whether the ends of the filaments are free or anchored to the bilayer. Computer simulations of the model reveal that curling, as experimentally observed, can be obtained either by an overall excess of weakly-bound filaments throughout the cell, or by the flux of such filaments toward the curling edges. Divalent cations have been shown to arrest the curling process, and Ca2+ ions have also been implicated in local membrane deformations during merozoite invasion. These effects can be replicated in our model by attributing the divalent cation effects to increased filament-membrane binding. This process converts the curl-inducing loose filaments into fully bound filaments that arrest curling. The same basic mechanism can be shown to account for Ca2+-induced local and dynamic membrane deformations in intact RBCs. The implications of these results in terms of RBC membrane dynamics under physiological, pathological, and experimental conditions is discussed.
authors.affiliation: Department of Chemical Physics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Kabaso
authors.forename: Roie
authors.initials: R
authors.lastname: Shlomovitz
authors.forename: Thorsten
authors.initials: T
authors.lastname: Auth
authors.forename: Virgilio L
authors.initials: VL
authors.lastname: Lew
authors.forename: Nir S
authors.initials: NS
authors.lastname: Gov
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002413:Cations, Divalent / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D013049:Spectrin / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D013049:Spectrin; D002118:Calcium