ArticleProceedings of the National Academy of Sciences of the United States of America2015
Multiple stiffening effects of nanoscale knobs on human red blood cells infected with Plasmodium falciparum malaria parasite.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 116 citations in OpenAlex.
- Detection of malaria infection from parasite-free blood smears.Malaria journal · 2026Article
- A periplasmic layer formed by an outer membrane lipoprotein governs the cell-envelope integrity and stiffness of Leptospira interrogans.Communications biology · 2026Article
- Deformability-augmented mesenchymal stem cells post-enucleation for efficient mRNA intervention of pulmonary fibrosis in rodent model.iScience · 2026Article
- A tutorial for mesoscale computer simulations of lipid membranes: tether pulling, tubulation and fluctuations.Soft matter · 2025Review
- Contact Dynamics of CytoadheringACS infectious diseases · 2025Article
- Biomechanics of phagocytosis of red blood cells by macrophages in the human spleen.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Exploring malaria parasite surface proteins to devise highly immunogenic multi-epitope subunit vaccine for Plasmodium falciparum.Journal, genetic engineering & biotechnology · 2024Article
- Molecular Rotors: Fluorescent Sensors for Microviscosity and Conformation of Biomolecules.Angewandte Chemie (International ed. in English) · 2024Review
- Knobs, Adhesion, and Severe Falciparum Malaria.Tropical medicine and infectious disease · 2023Review
- In silico modeling of patient-specific blood rheology in type 2 diabetes mellitus.Biophysical journal · 2023Article
- An update on cerebral malaria for therapeutic intervention.Molecular biology reports · 2022Review
- The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites.Traffic (Copenhagen, Denmark) · 2022Article
- A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections.PLoS computational biology · 2022Article
- Biophysical Tools and Concepts Enable Understanding of Asexual Blood Stage Malaria.Frontiers in cellular and infection microbiology · 2022Review
- Blood Viscosity in Subjects With Type 2 Diabetes Mellitus: Roles of Hyperglycemia and Elevated Plasma Fibrinogen.Frontiers in physiology · 2022Article
- How the spleen reshapes and retains young and old red blood cells: A computational investigation.PLoS computational biology · 2021Article
- Article
- Functionalized supported membranes for quantifying adhesion of P. falciparum-infected erythrocytes.Biophysical journal · 2021Article
- Surface area-to-volume ratio, not cellular viscoelasticity, is the major determinant of red blood cell traversal through small channels.Cellular microbiology · 2021Article
- Imaging non-classical mechanical responses of lipid membranes using molecular rotors.Chemical science · 2020Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During its asexual development within the red blood cell (RBC), Plasmodium falciparum (Pf), the most virulent human malaria parasite, exports proteins that modify the host RBC membrane. The attendant increase in cell stiffness and cytoadherence leads to sequestration of infected RBCs in microvasculature, which enables the parasite to evade the spleen, and leads to organ dysfunction in severe cases of malaria. Despite progress in understanding malaria pathogenesis, the molecular mechanisms responsible for the dramatic loss of deformability of Pf-infected RBCs have remained elusive. By recourse to a coarse-grained (CG) model that captures the molecular structures of Pf-infected RBC membrane, here we show that nanoscale surface protrusions, known as "knobs," introduce multiple stiffening mechanisms through composite strengthening, strain hardening, and knob density-dependent vertical coupling. On one hand, the knobs act as structural strengtheners for the spectrin network; on the other, the presence of knobs results in strain inhomogeneity in the spectrin network with elevated shear strain in the knob-free regions, which, given its strain-hardening property, effectively stiffens the network. From the trophozoite to the schizont stage that ensues within 24-48 h of parasite invasion into the RBC, the rise in the knob density results in the increased number of vertical constraints between the spectrin network and the lipid bilayer, which further stiffens the membrane. The shear moduli of Pf-infected RBCs predicted by the CG model at different stages of parasite maturation are in agreement with experimental results. In addition to providing a fundamental understanding of the stiffening mechanisms of Pf-infected RBCs, our simulation results suggest potential targets for antimalarial therapies.
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