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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-04-01
|
| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1009509 |
| _version_ | 1818479002951614464 |
|---|---|
| author | Julia Jäger Pintu Patra Cecilia P Sanchez Michael Lanzer Ulrich S Schwarz |
| author_facet | Julia Jäger Pintu Patra Cecilia P Sanchez Michael Lanzer Ulrich S Schwarz |
| author_sort | Julia Jäger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T09:55:21Z |
| format | Article |
| id | doaj.art-9996aa98a6bb48bb8f54bde4b91b2f5c |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-10T09:55:21Z |
| publishDate | 2022-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-9996aa98a6bb48bb8f54bde4b91b2f5c2022-12-22T01:53:32ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-04-01184e100950910.1371/journal.pcbi.1009509A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections.Julia JägerPintu PatraCecilia P SanchezMichael LanzerUlrich S SchwarzRed 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.https://doi.org/10.1371/journal.pcbi.1009509 |
| spellingShingle | Julia Jäger Pintu Patra Cecilia P Sanchez Michael Lanzer Ulrich S Schwarz A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections. PLoS Computational Biology |
| title | A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections. |
| title_full | A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections. |
| title_fullStr | A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections. |
| title_full_unstemmed | A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections. |
| title_short | A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections. |
| title_sort | particle based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections |
| url | https://doi.org/10.1371/journal.pcbi.1009509 |
| work_keys_str_mv | AT juliajager aparticlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT pintupatra aparticlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT ceciliapsanchez aparticlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT michaellanzer aparticlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT ulrichsschwarz aparticlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT juliajager particlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT pintupatra particlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT ceciliapsanchez particlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT michaellanzer particlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections AT ulrichsschwarz particlebasedcomputationalmodeltoanalyseremodellingoftheredbloodcellcytoskeletonduringmalariainfections |