Membrane-wrapping contributions to malaria parasite invasion of the human erythrocyte

Sabyasachi Dasgupta, Thorsten Auth, Nir S Gov, Timothy J Satchwell, Eric Hanssen, Elizabeth S Zuccala, David T Riglar, Ashley M Toye, Timo Betz, Jake Baum, Gerhard Gompper

Research output: Contribution to journalArticle (Academic Journal)peer-review

75 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)43-54
Number of pages12
JournalBiophysical Journal
Volume107
Issue number1
DOIs
Publication statusPublished - 1 Jul 2014

Bibliographical note

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Research Groups and Themes

  • Bristol BioDesign Institute

Keywords

  • synthetic biology

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