A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections
Red blood cells can withstand the harsh mechanical conditions in the vasculature only because the bending rigidity of their plasma membrane is complemented by the shear elasticity of the underlying spectrin-actin network. During an infection by the malaria parasite Plasmodium falciparum, the parasit...
Gespeichert in:
| Hauptverfasser: | , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) Kapitel/Artikel |
| Sprache: | Englisch |
| Veröffentlicht: |
October 4, 2021
|
| In: |
bioRxiv beta
Year: 2021, Pages: 1-30 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://www.biorxiv.org/content/10.1101/2021.10.04.462981v1
|
| Verfasserangaben: | Julia Jäger, Pintu Patra, Cecilia P. Sanchez, Michael Lanzer, Ulrich S. Schwarz |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1804090360 | ||
| 003 | DE-627 | ||
| 005 | 20221026132735.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220523s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2021.10.04.462981 |2 doi | |
| 035 | |a (DE-627)1804090360 | ||
| 035 | |a (DE-599)KXP1804090360 | ||
| 035 | |a (OCoLC)1341460379 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 29 |2 sdnb | ||
| 100 | 1 | |a Jäger, Julia |d 1991- |e VerfasserIn |0 (DE-588)1204938687 |0 (DE-627)1690240512 |4 aut | |
| 245 | 1 | 2 | |a A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections |c Julia Jäger, Pintu Patra, Cecilia P. Sanchez, Michael Lanzer, Ulrich S. Schwarz |
| 264 | 1 | |c October 4, 2021 | |
| 300 | |a 30 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 26.10.2022 | ||
| 520 | |a Red blood cells can withstand the harsh mechanical conditions in the vasculature only because the bending rigidity of their plasma membrane is complemented by the shear elasticity of the underlying spectrin-actin network. During an infection by the malaria parasite Plasmodium falciparum, the parasite mines host actin from the junctional complexes and establishes a system of adhesive knobs, whose main structural component is the knob-associated histidine rich protein (KAHRP) secreted by the parasite. Here we aim at a mechanistic understanding of this dramatic transformation process. We have developed a particle-based computational model for the cytoskeleton of red blood cells and simulated it with Brownian dynamics to predict the mechanical changes resulting from actin mining and KAHRP-clustering. Our simulations include the three-dimensional conformations of the semi-flexible spectrin chains, the capping of the actin protofilaments and several established binding sites for KAHRP. For the healthy red blood cell, we find that incorporation of actin protofilaments leads to two regimes in the shear response. Actin mining decreases the shear modulus, but knob formation increases it. We show that dynamical changes in KAHRP binding affinities can explain the experimentally observed relocalization of KAHRP from ankyrin to actin complexes and demonstrate good qualitative agreement with experiments by measuring pair cross-correlations both in the computer simulations and in super-resolution imaging experiments. - Author summary Malaria is one of the deadliest infectious diseases and its symptoms are related to the blood stage, when the parasite multiplies within red blood cells. In order to avoid clearance by the spleen, the parasite produces specific factors like the adhesion receptor PfEMP1 and the multifunctional protein KAHRP that lead to the formation of adhesive knobs on the surface of the red blood cells and thus increase residence time in the vasculature. We have developed a computational model for the parasite-induced remodelling of the actin-spectrin network to quantitatively predict the dynamical changes in the mechanical properties of the infected red blood cells and the spatial distribution of the different protein components of the membrane skeleton. Our simulations show that KAHRP can relocate to actin junctions due to dynamical changes in binding affinities, in good qualitative agreement with super-resolution imaging experiments. In the future, our simulation framework can be used to gain further mechanistic insight into the way malaria parasites attack the red blood cell cytoskeleton. | ||
| 700 | 1 | |a Patra, Pintu |e VerfasserIn |0 (DE-588)1194494048 |0 (DE-627)1676509607 |4 aut | |
| 700 | 1 | |a Sanchez, Cecilia P. |e VerfasserIn |0 (DE-588)1079241388 |0 (DE-627)840669348 |0 (DE-576)452286093 |4 aut | |
| 700 | 1 | |a Lanzer, Michael |e VerfasserIn |0 (DE-588)1065643314 |0 (DE-627)816506736 |0 (DE-576)165563826 |4 aut | |
| 700 | 1 | |a Schwarz, Ulrich S. |d 1966- |e VerfasserIn |0 (DE-588)120379473 |0 (DE-627)080637280 |0 (DE-576)297582763 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv beta |d Cold Spring Harbor : Cold Spring Harbor Laboratory, NY, 2013 |g (2021), Artikel-ID 2021.10.04.462981, Seite 1-30 |h Online-Ressource |w (DE-627)783307497 |w (DE-600)2766415-6 |w (DE-576)404299903 |7 nnas |a A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections |
| 773 | 1 | 8 | |g year:2021 |g elocationid:2021.10.04.462981 |g pages:1-30 |g extent:30 |a A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections |
| 856 | 4 | 0 | |u https://www.biorxiv.org/content/10.1101/2021.10.04.462981v1 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20220523 | ||
| 993 | |a Article | ||
| 998 | |g 120379473 |a Schwarz, Ulrich S. |m 120379473:Schwarz, Ulrich S. |d 130000 |d 130300 |d 700000 |d 728500 |e 130000PS120379473 |e 130300PS120379473 |e 700000PS120379473 |e 728500PS120379473 |k 0/130000/ |k 1/130000/130300/ |k 0/700000/ |k 1/700000/728500/ |p 5 |y j | ||
| 998 | |g 1065643314 |a Lanzer, Michael |m 1065643314:Lanzer, Michael |d 910000 |d 911700 |e 910000PL1065643314 |e 911700PL1065643314 |k 0/910000/ |k 1/910000/911700/ |p 4 | ||
| 998 | |g 1079241388 |a Sanchez, Cecilia P. |m 1079241388:Sanchez, Cecilia P. |d 910000 |d 911700 |e 910000PS1079241388 |e 911700PS1079241388 |k 0/910000/ |k 1/910000/911700/ |p 3 | ||
| 998 | |g 1194494048 |a Patra, Pintu |m 1194494048:Patra, Pintu |d 910000 |d 911700 |e 910000PP1194494048 |e 911700PP1194494048 |k 0/910000/ |k 1/910000/911700/ |p 2 | ||
| 998 | |g 1204938687 |a Jäger, Julia |m 1204938687:Jäger, Julia |p 1 |x j | ||
| 999 | |a KXP-PPN1804090360 |e 4138086811 | ||
| BIB | |a Y | ||
| JSO | |a {"relHost":[{"titleAlt":[{"title":"bio archive"}],"type":{"bibl":"edited-book","media":"Online-Ressource"},"recId":"783307497","physDesc":[{"extent":"Online-Ressource"}],"note":["Gesehen am 14.04.2014"],"origin":[{"publisher":"Cold Spring Harbor Laboratory, NY","publisherPlace":"Cold Spring Harbor","dateIssuedKey":"2013","dateIssuedDisp":"2013-"}],"part":{"pages":"1-30","extent":"30","text":"(2021), Artikel-ID 2021.10.04.462981, Seite 1-30","year":"2021"},"id":{"zdb":["2766415-6"],"eki":["783307497"]},"disp":"A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infectionsbioRxiv beta","title":[{"title":"bioRxiv beta","title_sort":"bioRxiv beta","subtitle":"the preprint server for biology"}],"language":["eng"],"pubHistory":["2013 -"]}],"physDesc":[{"extent":"30 S."}],"recId":"1804090360","note":["Gesehen am 26.10.2022"],"language":["eng"],"origin":[{"dateIssuedDisp":"October 4, 2021","dateIssuedKey":"2021"}],"id":{"doi":["10.1101/2021.10.04.462981"],"eki":["1804090360"]},"person":[{"role":"aut","display":"Jäger, Julia","family":"Jäger","given":"Julia"},{"display":"Patra, Pintu","role":"aut","family":"Patra","given":"Pintu"},{"given":"Cecilia P.","family":"Sanchez","display":"Sanchez, Cecilia P.","role":"aut"},{"given":"Michael","family":"Lanzer","role":"aut","display":"Lanzer, Michael"},{"family":"Schwarz","role":"aut","display":"Schwarz, Ulrich S.","given":"Ulrich S."}],"type":{"bibl":"chapter","media":"Online-Ressource"},"name":{"displayForm":["Julia Jäger, Pintu Patra, Cecilia P. Sanchez, Michael Lanzer, Ulrich S. Schwarz"]},"title":[{"title_sort":"particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections","title":"A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections"}]} | ||
| SRT | |a JAEGERJULIPARTICLEBA4202 | ||