Biology subjects

Fedosov, D. A.

Publications and source records attributed to Fedosov, D. A..

4 recordsLinked to original sources

bioRxiv2024

Aggregation and disaggregation of red blood cells: depletion versus bridging

The aggregation of red blood cells (RBCs) is a complex phenomenon that strongly impacts blood flow and tissue perfusion. Despite extensive research for more than 50 years, physical mechanisms that govern RBC aggregation are still under debate. Two proposed mechanisms are based on bridging and depletion interactions between RBCs due to the presence of macromolecules in blood plasma. The bridging hypothesis assumes the formation of bonds between RBCs through adsorbing macromolecules, while the depletion mechanism results from the exclusion of macromolecules from the inter-cellular space, leading to effective attraction. Existing experimental studies generally cannot differentiate between these two aggregation mechanisms, though several recent investigations suggest concurrent involvement of the both mechanisms. We explore dynamic aggregation and disaggregation of two RBCs using three simulation models: a potential-based model mimicking depletion interactions, a bridging model with immobile bonds, and a new bridging model with mobile bonds which can slide along RBC membranes. Simulation results indicate that dynamic aggregation of RBCs primarily arises from depletion interactions, while disaggregation of RBCs involves both mechanisms. The bridging model with mobile bonds reproduces well the corresponding experimental data, offering insights into the interplay between bridging and depletion interactions and providing a framework for studying similar interactions between other biological cells.

biophysics↗

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↗

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↗

bioRxiv2018

High-throughput microfluidic characterization of erythrocyte shape and mechanical variability

The motion of red blood cells (RBCs) in microchannels is important for microvascular blood flow and biomedical applications such as blood analysis in microfluidics. The current understanding of the complexity of RBC shapes and dynamics in microchannels is mainly based on several simulation studies, but there are a few systematic experimental investigations. Here, we present a combined study, which systematically characterizes RBC behavior for a wide range of flow rates and channel sizes. Even though simulations and experiments generally show good agreement, experimental observations demonstrate that there is no single well-defined RBC state for fixed flow conditions, but rather a broad distribution of states. This result can be attributed to the inherent variability in RBC mechanical properties, which is confirmed by a model that takes the variation in RBC shear elasticity into account. This represents a significant step toward a quantitative connection between RBC behavior in microfluidic devices and their mechanical properties, which is essential for a high-throughput characterization of diseased cells.\n\nSignificance StatementThe ability to change shape is crucial for the proper functioning of red blood cells under harsh conditions in the microvasculature, since their shapes strongly affect the flow behavior of whole blood. Our results from simulations and systematic experiments reveal the shapes and dynamics of red blood cells for different flow conditions and channel dimensions, generally in good agreement. However, in the experiments, cells do not exhibit a single well-defined shape for fixed flow conditions. We show that this distribution of shapes can be attributed to the variability in mechanical properties of red blood cells.

biophysics↗