Biology subjects

Fedosov, D.

Publications and source records attributed to Fedosov, D..

6 recordsLinked to original sources

bioRxiv2025

Trypanosomes Modulation of Motility from Swimming to Threading Propulsion in Confined Environments

Trypanosoma brucei (T. brucei) is a protozoan parasite that lives extracellularly in the body fluids of its hosts. In mammals, these environments include the vascular system and the interstitial spaces of various organs, such as the skin and adipose tissue. How the parasite disseminates within the host remains largely unresolved. It is clear however, that parasite motility plays a central role. The unicellular, eukaryotic flagellate is a versatile microswimmer, like bacteria or sperm cells, albeit structurally far more complex than these classical model systems. In addition to possessing a flagellum attached alongside a strongly polarised cell body, the parasite is capable of swimming both forwards and backwards. The trypanosome must be capable of navigating effectively even under extreme physical and mechanical constraints. It can do so in the mammalian host with only one main morphotype. This means that the cell is mechanically adapted to motion in diverse challenging microenvironments. To address how, we study the parasites in different viscoelastic regimes up to conditions mimicking tissue confinement. Next to quantitative high speed video microscopy, we employ digital holography microscopy, yielding three-dimensional subcellular resolution. We detail the mechanical reaction of the flexible cell body with its uniquely attached flagellum to increasing confinement and show how the trypanosomes are able to maintain their motile capabilities to spread in dense tissue.

microbiology↗

bioRxiv2025

Binding of extracellular vesicles to stretched von Willebrand factor promotes platelet activation

Von Willebrand factor (vWF), promoting platelet aggregation in various diseases such as COVID-19, malaria and cancer, is a huge multimeric glycoprotein. This extraordinary size makes vWF a unique shear stress sensing molecule. Below a critical shear stress, vWF is in a globular conformation that prevents platelet binding. Above the critical shear stress, vWF is stretched into platelet accessible fibers. Although previous studies have suggested that leukocytes or cancer cells can bind to vWF fibers, acting forces and the likelihood of cell adhesion has remained largely unexplored. Here, we report that vWF is a size-selective protein that prefers to interact with objects smaller than 4 m in diameter. Consistently, tumor cell-derived extracellular vesicles (EVs) were able to interact with vWF in parallel to platelets. Although whole tumor cells under flow were unable to bind to vWF per se, binding of EVs and platelets along the vWF fiber promoted platelet aggregation, which in turn entrapped circulating tumor cells. In conclusion, our study highlights the shear-sensitive nature of vWF and its ability to bring EVs and platelets together to enhance coagulation. While EVs-vWF-platelet aggregates may serve as novel biomarkers, their therapeutic disruption may prevent hypercoagulation in disease.

cancer biology↗

bioRxiv2025

Run-and-tumble dynamics of E. coli is governed by its mechanical properties

The huge variety of microorganisms motivates fundamental studies of their behavior with a possibility to construct artificial mimics. A prominent example is the E. coli bacterium which employs several helical flagella to exhibit a motility pattern that alternates between run (directional swimming) and tumble (change in swimming direction) phases. We establish a detailed E. coli model, coupled to fluid flow described by the dissipative particle dynamics method, and investigate its run-and-tumble behavior. Different E. coli characteristics, including body geometry, flagella bending rigidity, the number of flagella and their arrangement at the body are considered. Experiments are also performed to directly compare with the model. Interestingly, in both simulations and experiments, the swimming velocity is nearly independent of the number of flagella. The rigidity of a hook (the short part of a flagellum which connects it directly to the motor), polymorphic transformation (spontaneous change in flagella helicity) of flagella, and their arrangement at the body surface strongly influence the run-and-tumble behavior. Mesoscale hydrodynamics simulations with the developed model help us better understand physical mechanisms which govern E. coli dynamics, yielding the run-and-tumble behavior that compares well with experimental observations. This model can further be used to explore the behavior of E. coli and other peritrichous bacteria in more complex realistic environments.

biophysics↗

bioRxiv2024

Modelling trypanosome motility

African trypanosomiasis, or sleeping sickness, is a life-threatening disease caused by the protozoan parasite Trypanosoma brucei. The bloodstream form of T. brucei has a slender body with a relatively long active flagellum, which makes it an excellent swimmer. We develop a realistic trypanosome model and perform mesoscale hydrodynamic simulations to study the importance of various mechanical characteristics for trypanosome swimming behavior. The cell body is represented by an elastic triangulated network, while the attached flagellum consists of four interconnected running-in-parallel filaments, which permits a good control of the flagellum beating plane. Our simulation results are validated against experimental observations, and highlight the crucial role of body elasticity, non-uniform actuation along the flagellum length, and the orientation of flagellum-beating plane with respect to the body surface for trypanosome locomotion. These results offer a framework for exploring parasite behavior in complex environments.

biophysics↗

bioRxiv2021

Importance of viscosity contrast for the motion of erythrocytes in microcapillaries

The dynamics and deformation of red blood cells (RBCs) in microcirculation affect the flow resistance and transport properties of whole blood. One of the key properties that can alter RBC dynamics in flow is the contrast {lambda} (or ratio) of viscosities between RBC cytosol and blood plasma. Here, we study the dependence of RBC shape and dynamics on the viscosity contrast in tube flow, using mesoscopic hydrodynamics simulations. State diagrams of different RBC dynamical states, including tumbling cells, parachutes, and tank-treading slippers, are constructed for various viscosity contrasts and wide ranges of flow rates and tube diameters (or RBC confinements). Despite similarities in the classification of RBC behavior for different viscosity contrasts, there are notable differences in the corresponding state diagrams. In particular, the region of parachutes is significantly larger for {lambda} = 1 in comparison to {lambda} = 5. Furthermore, the viscosity contrast strongly affects the tumbling-to-slipper transition, thus modifying the regions of occurrence of these states as a function of flow rate and RBC confinement. Also, an increase in cytosol viscosity leads to a reduction in membrane tension induced by flow stresses. Physical mechanisms that determine these differences in RBC dynamical states as a function of {lambda} are discussed.

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↗