Abstract
Invasion of erythrocytes by merozoites is an essential step for the survival and progression of malaria parasites. To invade red blood cells (RBCs), apicomplexan parasites have to adhere with their apex to the RBC membrane. This necessary apex-membrane contact (or alignment) is not immediately established because the orientation of a free merozoite with respect to the RBC membrane is random when an adhesion contact first occurs. Therefore, it has been suggested that after the initial adhesion, merozoites facilitate their proper alignment by inducing considerable membrane deformations, frequently observed before the invasion process. This proposition is based on a positive correlation between RBC membrane deformation and successful invasion; however, the role of RBC mechanics and its deformation in the alignment process remains elusive. Using a mechanically realistic model of a deformable RBC, we investigate numerically the importance of RBC deformability for merozoite alignment. Adhesion between the parasite and RBC membrane is modeled by an attractive potential that might be inhomogeneous, mimicking possible adhesion gradients at the surface of a parasite. Our results show that RBC membrane deformations are crucial for successful merozoite alignment and require interaction strengths comparable to adhesion forces measured experimentally. Adhesion gradients along the parasite body further improve its alignment. Finally, an increased membrane rigidity is found to result in poor merozoite alignment, which can be a possible reason for a reduction in the invasion susceptibility of RBCs in several blood diseases associated with membrane stiffening.
Highlights
Malaria remains one of the most devastating diseases in the world, especially in African and South Asian regions, claiming over 400,000 lives per year [1]
Our results show that the parasite-red blood cells (RBCs) adhesion interactions, whose strength is comparable with experimentally measured adhesion forces [9], produce membrane deformations of various intensity, qualitatively matching experimental observations [11,12,13,14,18]
Our simulation results support the passive compliance hypothesis [20], which states that the alignment of merozoites arises from mechanical adhesion interactions between the parasite and RBC and induced membrane deformations
Summary
It is hypothesized that merozoites are able to facilitate the alignment of their apex toward the RBC membrane after their initial adhesion with a random orientation [10]. This alignment or preinvasion stage occurs within the range of 2–50 s [10,11,12], which is fast enough to proceed to RBC invasion afterwards. A recent experimental study [18] has suggested that a positive correlation between the magnitude of membrane deformations and the efficiency of RBC invasion exists Such membrane deformations subside right after the alignment is achieved and the merozoite starts initiating cell invasion. The importance of RBC membrane deformation for parasite alignment is discussed
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