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

Dearnley Megan; Chu Trang; Zhang YaoLooker OliverHuang ChangjinKlonis NectariosYeoman JeffKenny ShannonArora MohitOsborne James M.Chandramohanadas RajeshZhang SulinDixon Matthew W. A.Tilley Leann

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

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

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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 photo-bleaching 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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2016年第17期|4800-4805|共6页
作者
Dearnley Megan; Chu Trang; Zhang YaoLooker OliverHuang ChangjinKlonis NectariosYeoman JeffKenny ShannonArora MohitOsborne James M.Chandramohanadas RajeshZhang SulinDixon Matthew W. A.Tilley Leann;
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作者单位

Univ Melbourne, Dept Biochem & Mol Biol, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia;

Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA;

La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, AustraliaSingapore Univ Technol & Design, Pillar Engn Prod Dev, Singapore 487372, SingaporeUniv Melbourne, Sch Math & Stat, Melbourne, Vic 3010, Australia;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
gametocyte; deformability; spectrin/actin skeleton; AFM; molecular dynamics simulation;

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

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