title: Membrane-wrapping contributions to malaria parasite invasion of the human erythrocyte.
abstract: The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade a human erythrocyte. The process of invasion is nonetheless remarkably rapid. To date, mechanistic models of invasion have focused predominantly on the parasite actomyosin motor contribution to the energetics of entry. Here, we have conducted a numerical analysis using dimensions for an archetypal merozoite to predict the respective contributions of the host-parasite interactions to invasion, in particular the role of membrane wrapping. Our theoretical modeling demonstrates that erythrocyte membrane wrapping alone, as a function of merozoite adhesive and shape properties, is sufficient to entirely account for the first key step of the invasion process, that of merozoite reorientation to its apex and tight adhesive linkage between the two cells. Next, parasite-induced reorganization of the erythrocyte cytoskeleton and release of parasite-derived membrane can also account for a considerable energetic portion of actual invasion itself, through membrane wrapping. Thus, contrary to the prevailing dogma, wrapping by the erythrocyte combined with parasite-derived membrane release can markedly reduce the expected contributions of the merozoite actomyosin motor to invasion. We therefore propose that invasion is a balance between parasite and host cell contributions, evolved toward maximal efficient use of biophysical forces between the two cells.
authors.affiliation: Institute of Complex Systems and Institute for Advanced Simulation, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Dasgupta
authors.affiliation: Institute of Complex Systems and Institute for Advanced Simulation, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Auth
authors.affiliation: Department of Chemical Physics, Weizmann Institute of Science, Rehovot, Israel; Centre de Recherche, Institut Curie, Paris, France.
authors.forename: Nir S
authors.initials: NS
authors.lastname: Gov
authors.affiliation: School of Biochemistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Satchwell
authors.affiliation: Advanced Microscopy Facility, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Eric
authors.initials: E
authors.lastname: Hanssen
authors.affiliation: Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Zuccala
authors.affiliation: Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: David T
authors.initials: DT
authors.lastname: Riglar
authors.affiliation: School of Biochemistry, University of Bristol, Bristol, United Kingdom; Bristol Institute for Transfusion Sciences, NHS Blood and Transplant, Bristol, United Kingdom.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Toye
authors.affiliation: Centre de Recherche, Institut Curie, Paris, France.
authors.forename: Timo
authors.initials: T
authors.lastname: Betz
authors.affiliation: Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom. Electronic address: jake.baum@imperial.ac.uk.
authors.forename: Jake
authors.initials: J
authors.lastname: Baum
authors.affiliation: Institute of Complex Systems and Institute for Advanced Simulation, Forschungszentrum Jülich, Jülich, Germany. Electronic address: g.gompper@fz-juelich.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gompper
mesh_terms: D002462:Cell Membrane / Q000378:metabolism / Q000469:parasitology*; D003599:Cytoskeleton / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D052940:Merozoites / Q000502:physiology; D010963:Plasmodium falciparum / Q000472:pathogenicity*