title: Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages.
abstract: The sexual blood stage of the human malaria parasite Plasmodium falciparum undergoes remarkable biophysical changes as it prepares for transmission to mosquitoes. During maturation, midstage gametocytes show low deformability and sequester in the bone marrow and spleen cords, thus avoiding clearance during passage through splenic sinuses. Mature gametocytes exhibit increased deformability and reappear in the peripheral circulation, allowing uptake by mosquitoes. Here we define the reversible changes in erythrocyte membrane organization that underpin this biomechanical transformation. Atomic force microscopy reveals that the length of the spectrin cross-members and the size of the skeletal meshwork increase in developing gametocytes, then decrease in mature-stage gametocytes. These changes are accompanied by relocation of actin from the erythrocyte membrane to the Maurer's clefts. Fluorescence recovery after photobleaching reveals reversible changes in the level of coupling between the membrane skeleton and the plasma membrane. Treatment of midstage gametocytes with cytochalasin D decreases the vertical coupling and increases their filterability. A computationally efficient coarse-grained model of the erythrocyte membrane reveals that restructuring and constraining the spectrin meshwork can fully account for the observed changes in deformability.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia;
authors.forename: Megan
authors.initials: M
authors.lastname: Dearnley
authors.affiliation: Pillar of Engineering Product Development, Singapore University of Technology and Design, Singapore 487372;
authors.forename: Trang
authors.initials: T
authors.lastname: Chu
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia;
authors.forename: Oliver
authors.initials: O
authors.lastname: Looker
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
authors.forename: Changjin
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia;
authors.forename: Nectarios
authors.initials: N
authors.lastname: Klonis
authors.affiliation: Department of Biochemistry, La Trobe University, Melbourne, VIC 3086, Australia;
authors.forename: Jeff
authors.initials: J
authors.lastname: Yeoman
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia;
authors.forename: Shannon
authors.initials: S
authors.lastname: Kenny
authors.affiliation: Pillar of Engineering Product Development, Singapore University of Technology and Design, Singapore 487372;
authors.forename: Mohit
authors.initials: M
authors.lastname: Arora
authors.affiliation: School of Mathematics and Statistics, University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: James M
authors.initials: JM
authors.lastname: Osborne
authors.affiliation: Pillar of Engineering Product Development, Singapore University of Technology and Design, Singapore 487372;
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chandramohanadas
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
authors.forename: Sulin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia;
authors.forename: Matthew W A
authors.initials: MW
authors.lastname: Dixon
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia; ltilley@unimelb.edu.au.
authors.forename: Leann
authors.initials: L
authors.lastname: Tilley
mesh_terms: D000199:Actins / Q000648:ultrastructure; D003198:Computer Simulation; D003599:Cytoskeleton / Q000648:ultrastructure; D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000648:ultrastructure*; D008018:Life Cycle Stages; D008870:Microtubules / Q000648:ultrastructure*; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000648:ultrastructure*; D013049:Spectrin / Q000648:ultrastructure
chemical_list: D000199:Actins; D013049:Spectrin
keywords: AFM; deformability; gametocyte; molecular dynamics simulation; spectrin/actin skeleton