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

Abstract In malaria infection, early eryptosis eliminates the protective niche provided by the infected erythrocyte, thus potentially interfering with the parasite’s 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 µN/m to 131 µN/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.