Biology subjects

Hillringhaus, S.

Publications and source records attributed to Hillringhaus, S..

3 recordsLinked to original sources

bioRxiv2021

Effect of malaria parasite shape on its alignment at erythrocyte membrane

During the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasites apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically un-favorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasites shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, spherical parasite aligns faster than any other investigated shapes. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes, but is more robust with respect to different adhesion interactions and RBC membrane rigidities.

biophysics↗

bioRxiv2020

Stochastic bond dynamics facilitates alignment of malaria parasite at erythrocyte membrane upon invasion

Malaria parasites invade healthy red blood cells (RBCs) during the blood stage of the disease. Even though parasites initially adhere to RBCs with a random orientation, they need to align their apex toward the membrane in order to start the invasion process. Using hydrodynamic simulations of a RBC and parasite, where both interact through discrete stochastic bonds, we show that parasite alignment is governed by the combination of RBC membrane deformability and dynamics of adhesion bonds. The stochastic nature of bond-based interactions facilitates a diffusive-like re-orientation of the parasite at the RBC membrane, while RBC deformation aids in the establishment of apexmembrane contact through partial parasite wrapping by the membrane. This bond-based model for parasite adhesion quantitatively captures alignment times measured experimentally and demonstrates that alignment times increase drastically with increasing rigidity of the RBC membrane. Our results suggest that the alignment process is mediated simply by passive parasite adhesion.

biophysics↗

bioRxiv2019

Importance of erythrocyte deformability for the alignment of malaria parasite upon invasion

Invasion of erythrocytes by merozoites is an essential step for the survival and progression of malaria parasites. In order to invade red blood cells (RBCs), parasites have to adhere with their apex to the RBC membrane. Since a random adhesion contact between the parasite and membrane would be too inefficient, it has been hypothesized that merozoites are able to actively re-orient toward apex-membrane alignment. This is supported by several experimental observations which show that merozoites frequently induce considerable membrane deformations before the invasion process. Even though a positive correlation between RBC membrane deformation and successful invasion is established, 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 which 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 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 the reduction in the invasion of RBCs in several blood diseases associated with membrane stiffening.\n\nSTATEMENT OF SIGNIFICANCEPlasmodium parasites invade erythrocytes during the progression of malaria. To start invasion, the parasites have to re-orient themselves such that their apex establishes a direct contact with erythrocyte membrane. The re-orientation (or alignment) process is often associated with strong membrane deformations, which are believed to be induced by the parasite and are positively correlated with its alignment. We employ a mechanically realistic erythrocyte model to investigate the interplay of membrane deformations and merozoite alignment during parasite adhesion to an erythrocyte. Our model clearly demonstrates that erythrocyte membrane deformations are a key component of successful parasite alignment, since the re-orientation of parasites at rigidified membranes is generally poor. Therefore, our results suggest a possible mechanism for the reduction in erythrocyte invasion in several blood diseases associated with membrane stiffening.

biophysics↗