Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages

Megan Dearnley, Trang Chu, Yao Zhang, Oliver Looker, Changjin Huang, Nectarios Klonis, Jeff Yeoman, Shannon Kenny, Mohit Arora, James M. Osborne, Rajesh Chandramohanadas, Sulin Zhang, Matthew W.A. Dixon, Leann Tilley

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


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 crossmembers 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.

Original languageEnglish (US)
Pages (from-to)4800-4805
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
StatePublished - Apr 26 2016

All Science Journal Classification (ASJC) codes

  • General


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