Biology subjects

Msosa, C.

Publications and source records attributed to Msosa, C..

3 recordsLinked to original sources

bioRxiv2024

Computational analysis of the plasmodium falciparum-induced intraerythrocyte deformations: insights into malaria parasite egress mechanics and eryptosis

In malaria infection, early eryptosis eliminates the protective niche provided by the infected erythrocyte, thus potentially interfering with the parasites survival rate in the human host, consequently presenting a putative target mechanism for antimalarial therapeutic interventions. The malaria parasite-induced oxidative stress is the primary trigger of eryptosis. Despite being barely investigated, erythrocyte membrane mechanical deformations induced by the malaria parasites during the intraerythrocyte development stage, represent a potential eryptosis trigger. A finite element model of the plasmodium falciparum-infected erythrocyte was developed and calibrated in Abaqus using pre-determined optical tweezer data of the trophozoite-infected erythrocyte. The developed model computationally predicts mechanistic correlations between erythrocyte membrane areal strain, eryptosis, erythrocyte membrane shear modulus and the volume fraction of malaria parasites in the infected erythrocyte. The model predicts the erythrocyte membrane areal strain of 3.1 % at the established rupture volume fraction (VF) of 83%, which falls within the pre-determined erythrocyte membrane lysis threshold of 2-4 %. When the erythrocyte membrane in-plane shear modulus is increased from 2.84 {micro}N/m to 131 {micro}N/m, the erythrocyte areal strain increases from 1.55 % to 3.2 % at the same rupture volume fraction (VF) of 83% implying that increasing the erythrocyte membrane stiffness during the malaria intra-erythrocytic development stage can potentially induce early lysis while decreasing the erythrocyte membrane stiffness can potentially induce late lysis. Understanding the mechanisms governing the exit of malaria parasites from infected erythrocytes during the late schizont stage is crucial for developing effective therapeutic interventions. Existing studies lack a comprehensive exploration of how malaria parasite-induced remodelling affects the areal strain of the erythrocyte membrane. Experimental challenges in studying infected erythrocytes have limited progress, making computational models a valuable tool. This research provides valuable insights into the mechanics of malaria-induced erythrocyte remodelling, offering a computational framework for studying parasite egress to inform potential therapeutic strategies.

biophysics↗

bioRxiv2023

A constitutive model for the remodelling erythrocyte membrane skeleton during the active invasion by the malaria merozoite

Malaria merozoites phosphorylate erythrocyte membrane proteins to breach the membrane during invasion. This study aimed to develop a constitutive model for erythrocyte membrane phosphorylation that reduces the membranes elastic modulus and resistance to merozoite invasion. The hyperelastic Mooney Rivlin constitutive model was adapted by adding an exponential term to represent the mechanical effect of erythrocyte membrane phosphorylation. The modified algorithm was verified with the unmodified Mooney Rivlin model for the intact erythrocyte membrane and used to predict erythrocyte membrane stress for equi-biaxial membrane strain up to 1.1 for different severity of phosphorylation damage. The stability of the damage model was assessed using the Drucker criterion for equi-biaxial strain up to 2.0. Strain and stress predicted with the developed damage model and the Mooney Rivlin model agreed for the intact erythrocyte membrane. The membrane stress at a strain of 1.1 decreased by 42% for minor and 95% for severe erythrocyte membrane damage. The stability strain threshold of the damage model was 1.98 for minor and 1.19 for severe membrane damage. The developed model can represent different degrees of erythrocyte membrane damage through phosphorylation by a malaria merozoite. The model will enable in silico investigations of the invasiveness of malaria merozoites.

biophysics↗

bioRxiv2022

An analytical model describing the mechanics of erythrocyte membrane wrapping during active invasion of a plasmodium falciparum merozoite

The invasion of a merozoite into an erythrocyte by membrane wrapping is a hallmark of malaria pathogenesis. The invasion involves biomechanical interactions whereby the merozoite exerts actomyosin-based forces to push itself into and through the erythrocyte membrane while concurrently inducing biochemical damage to the erythrocyte membrane. Whereas the biochemical damage process has been investigated, the detailed mechanistic understanding of the invasion mechanics remains limited. Thus, the current study aimed to develop a mathematical model describing the mechanical factors involved in the merozoite invasion into an erythrocyte and explore the invasion mechanics. A shell theory model was developed comprising constitutive, equilibrium and governing equations of the deformable erythrocyte membrane to predict membrane mechanics during the wrapping of an entire non-deformable ellipsoidal merozoite. Predicted parameters include principal erythrocyte membrane deformations and stresses, wrapping and indentation forces, and indentation work. The numerical investigations considered two limits for the erythrocyte membrane deformation during wrapping (4% and 51% areal strain) and erythrocyte membrane phosphorylation (decrease of membrane elastic modulus from 1 to 0.5 kPa). For an intact erythrocyte, the maximum indentation force was 1 and 8.5 pN, and the indentation work was 1.92 x10-18 and 1.40 x10-17 J for 4% and 51% areal membrane strain. Phosphorylation damage in the erythrocyte membrane reduced the required indentation work by 50% to 0.97 x10-18 and 0.70 x10-17 J for 4% and 51% areal strain. The current study demonstrated the developed models feasibility to provide new knowledge on the physical mechanisms of the merozoite invasion process that contribute to the invasion efficiency towards the discovery of new invasion-blocking anti-malaria drugs.

biophysics↗