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Dmitry A. Fedosov

Publications and source records attributed to Dmitry A. Fedosov.

At least 19 recordsLinked to original sources

Trypanosome motility in blood and particle suspensions

Motile microorganisms often navigate crowded and structurally complex environments, where surrounding obstacles can strongly influence locomotion. The bloodstream form of the flagellate parasite Trypanosoma brucei circulates in blood, a dense suspension of red blood cells (RBCs), yet the physical mechanisms governing its locomotion under such conditions remain poorly understood because direct experimental observations are challenging. Here, we combine numerical simulations with in vitro experiments to investigate trypanosome motility in concentrated RBC suspensions and in suspensions of spherical colloidal particles. Simulations reveal that the parasite swimming speed increases by up to $50\%$ at RBC volume fractions comparable to those in blood. To identify the origin of this enhancement, we perform controlled studies in colloidal suspensions with particles of different sizes. We find that suspended particles substantially increase the anisotropy between the perpendicular and parallel friction coefficients acting on the beating flagellum, thereby enhancing propulsion. This effect is most pronounced when the suspended particles are comparable to or smaller than the characteristic wavelength of the flagellar beat. Experiments with microparticle suspensions confirm an increase in trypanosome propulsion with increasing particle concentration, in qualitative agreement with the simulations. Our results uncover a general physical mechanism by which concentrated particle suspensions can enhance flagellar-beat-driven locomotion and suggest that the densely crowded, particulate environment of blood may facilitate trypanosome propulsion. These findings provide new insight into trypanosome motility in the bloodstream and may apply broadly to other flagellated microswimmers in complex suspensions.

physics.bio-ph↗

Primary hemostasis and dynamics of clot formation after microvascular injury

Primary hemostasis is initiated by platelet adhesion and aggregation at a site of vascular injury and is strongly regulated by local hydrodynamic conditions. At elevated shear rates, platelet capture is mediated by von Willebrand factor (vWF), a multimeric protein that undergoes shear-induced unfolding and becomes adhesive. We investigate early-stage clot formation under physiological high-shear-flow conditions by employing particle-based mesoscale hydrodynamics simulations with explicitly resolved red blood cells, platelets, and mechano-sensitive vWF in a microchannel geometry. The model incorporates vWF-mediated adhesion of platelets to a hemostatic surface, together with non-periodic inflow-outflow boundary conditions that allow continuous material supply and transport. We analyze the dynamics of platelet-vWF aggregation, clot growth dynamics, clot geometry and internal stresses, and thrombo-embolization across a range of elevated flow rates. Our results demonstrate that clot formation proceeds through the establishment of platelet-vWF aggregates at the hemostatic site, and that the clot reaches a finite size determined solely by hydrodynamic forces, without invoking biochemical stabilization mechanisms. Beyond a critical size, increased drag from fluid flow leads to recurrent embolization events that limit further growth. These findings highlight the central role of hydrodynamic stresses in regulating primary hemostasis and provide a mechanistic framework for understanding clot stability under physiological flow conditions.

physics.bio-ph↗

The 2024 Motile Active Matter Roadmap

Activity and autonomous motion are fundamental aspects of many living and engineering systems. Here, the scale of biological agents covers a wide range, from nanomotors, cytoskeleton, and cells, to insects, fish, birds, and people. Inspired by biological active systems, various types of autonomous synthetic nano- and micromachines have been designed, which provide the basis for multifunctional, highly responsive, intelligent active materials. A major challenge for understanding and designing active matter is their inherent non-equilibrium nature due to persistent energy consumption, which invalidates equilibrium concepts such as free energy, detailed balance, and time-reversal symmetry. Furthermore, interactions in ensembles of active agents are often non-additive and non-reciprocal. An important aspect of biological agents is their ability to sense the environment, process this information, and adjust their motion accordingly. It is an important goal for the engineering of micro-robotic systems to achieve similar functionality. With many fundamental properties of motile active matter now reasonably well understood and under control, the ground is prepared for the study of physical aspects and mechanisms of motion in complex environments, of the behavior of systems with new physical features like chirality, of the development of novel micromachines and microbots, of the emergent collective behavior and swarming of intelligent self-propelled particles, and of particular features of microbial systems. The vast complexity of phenomena and mechanisms involved in the self-organization and dynamics of motile active matter poses major challenges, which can only be addressed by a truly interdisciplinary effort involving scientists from biology, chemistry, ecology, engineering, mathematics, and physics.

cond-mat.soft↗

Collective behavior of squirmers in thin films

Bacteria in biofilms form complex structures and can collectively migrate within mobile aggregates, which is referred to as swarming. This behavior is influenced by a combination of various factors, including morphological characteristics and propulsive forces of swimmers, their volume fraction within a confined environment, and hydrodynamic and steric interactions between them. In our study, we employ the squirmer model for microswimmers and the dissipative particle dynamics method for fluid modeling to investigate the collective motion of swimmers in thin films. The film thickness permits a free orientation of non-spherical squirmers, but constraints them to form a two-layered structure at maximum. Structural and dynamic properties of squirmer suspensions confined within the slit are analyzed for different volume fractions of swimmers, motility types (e.g., pusher, neutral squirmer, puller), and the presence of a rotlet dipolar flow field, which mimics the counter-rotating flow generated by flagellated bacteria. Different states are characterized, including a gas-like phase, swarming, and motility-induced phase separation, as a function of increasing volume fraction. Our study highlights the importance of an anisotropic swimmer shape, hydrodynamic interactions between squirmers, and their interaction with the walls for the emergence of different collective behaviors. Interestingly, the formation of collective structures may not be symmetric with respect to the two walls. Furthermore, the presence of a rotlet dipole significantly mitigates differences in the collective behavior between various swimmer types. These results contribute to a better understanding of the formation of bacterial biofilms and the emergence of collective states in confined active matter.

cond-mat.soft↗

Motion of microswimmers in cylindrical microchannels

Biological and artificial microswimmers often have to propel through a variety of environments, ranging from heterogeneous suspending media to strong geometrical confinement. Under confinement, local flow fields generated by microswimmers, and steric and hydrodynamic interactions with their environment determine the locomotion. We propose a squirmer-like model to describe the motion of microswimmers in cylindrical microchannels, where propulsion is generated by a fixed surface slip velocity. The model is studied analytically for cylindrical swimmer shapes, and by numerical hydrodynamics simulations for spherical and spheroidal shapes. For the numerical simulations, we employ the dissipative particle dynamics method for modelling fluid flow. Both the analytical model and simulations show that the propulsion force increases with increasing confinement. However, the swimming velocity under confinement remains lower than the swimmer speed without confinement for all investigated conditions. In simulations, different swimming modes (i.e. pusher, neutral, puller) are investigated, and found to play a significant role in the generation of propulsion force when a swimmer approaches a dead end of a capillary. Propulsion generation in confined systems is local, such that the generated flow field generally vanishes beyond the characteristic size of the swimmer. These results contribute to a better understanding of microswimmer force generation and propulsion under strong confinement, including the motion in porous media and in narrow channels.

cond-mat.soft↗

Dynamic shapes of floppy vesicles enclosing active Brownian particles with membrane adhesion

Recent advances in micro- and nano-technologies allow the construction of complex active systems from biological and synthetic materials. An interesting example is active vesicles, which consist of a membrane enclosing self-propelled particles, and exhibit several features resembling biological cells. We investigate numerically the behavior of active vesicles, where the enclosed self-propelled particles can adhere to the membrane. A vesicle is represented by a dynamically triangulated membrane, while the adhesive active particles are modelled as active Brownian particles (ABPs) that interact with the membrane via the Lennard-Jones potential. Phase diagrams of dynamic vesicle shapes as a function of ABP activity and particle volume fraction inside the vesicle are constructed for different strengths of adhesive interactions. At low ABP activity, adhesive interactions dominate over the propulsion forces, such that the vesicle attains near static configurations, with protrusions of membrane-wrapped ABPs having ring-like and sheet-like structures. At moderate particle densities and strong enough activities, active vesicles show dynamic highly-branched tethers filled with string-like arrangements of ABPs, which do not occur in the absence of particle adhesion to the membrane. At large volume fractions of ABPs, vesicles fluctuate for moderate particle activities, and elongate and finally split into two vesicles for large ABP propulsion strengths. We also analyze membrane tension, active fluctuations, and ABP characteristics (e.g., mobility, clustering), and compare them to the case of active vesicles with non-adhesive ABPs. The adhesion of ABPs to the membrane significantly alters the behavior of active vesicles, and provides an additional parameter for controlling their behavior.

cond-mat.soft↗

Phase separation of active Brownian particles on curved surfaces

The effect of curvature on an ensemble of repulsive active Brownian particles (ABPs) moving on a spherical surface is studied. Surface curvature strongly affects the dynamics of ABPs, as it introduces a new time scale $τ=R/v_0$, with curvature radius $R$ and propulsion velocity $v_0$, in addition to the rotational diffusion time $τ_r$. This implies that motility-induced phase separation (MIPS) disappears for small $R$. Furthermore, it causes a narrowing of the MIPS regime in the phase diagram of P{é}clet number $\text{Pe}$ and particle area fraction $ϕ$. Also, the phase-separation boundary at low $ϕ$ attains a turning point at small $R$, allowing for the possibility of a reentrant behavior. These results characterize the effect of curvature on ABP dynamics and MIPS, and will help to better understand the preferred occupation of certain niches by bacterial colonies in porous media.

cond-mat.soft↗

Erythrocyte sedimentation: Effect of aggregation energy on gel structure during collapse

The erythrocyte (or red blood cell) sedimentation rate (ESR) is commonly interpreted as a measure of cell aggregation and as a biomarker of inflammation. It is well known that an increase of fibrinogen concentration, an aggregation-inducing protein for erythrocytes, leads to an increase of the sedimentation rate of erythrocytes, which is generally explained through the formation and faster settling of large disjoint aggregates. However, many aspects of erythrocyte sedimentation conform well with the collapse of a colloidal gel rather than with the sedimentation of disjoint aggregates. Using experiments and cell-level numerical simulations, we systematically investigate the dependence of ESR on fibrinogen concentration and its relation to the microstructure of the gel-like erythrocyte suspension. We show that for physiological aggregation interactions, an increase in the attraction strength between cells results in a cell network with larger void spaces. This geometrical change in the network structure occurs due to anisotropic shape and deformability of erythrocytes and leads to an increased gel permeability and faster sedimentation. Our results provide a comprehensive relation between the ESR and the cell-level structure of erythrocyte suspensions and support the gel hypothesis in the interpretation of blood sedimentation.

cond-mat.soft↗

Erythrocyte sedimentation: Fracture and collapse of a high-volume-fraction soft-colloid gel

The erythrocyte sedimentation rate is one of the oldest medical diagnostic methods whose physical mechanisms remain debatable up to date. Using both light microscopy and mesoscale cell-level simulations, we show that erythrocytes form a soft-colloid gel. Furthermore, the high volume fraction of erythrocytes, their deformability, and weak attraction lead to unusual properties of this gel. A theoretical model for the gravitational collapse is developed, whose predictions are in agreement with detailed macroscopic measurements of the interface velocity.

cond-mat.soft↗

Stability of heterogeneous parallel-bond adhesion clusters under static load

Adhesion interactions mediated by multiple bond types are relevant for many biological and soft matter systems, including the adhesion of biological cells and functionalized colloidal particles to various substrates. To elucidate advantages and disadvantages of multiple bond populations for the stability of heterogeneous adhesion clusters of receptor-ligand pairs, a theoretical model for a homogeneous parallel adhesion bond cluster under constant loading is extended to several bond types. The stability of the entire cluster can be tuned by changing densities of different bond populations as well as their extensional rigidity and binding properties. In particular, bond extensional rigidities determine the distribution of total load to be shared between different sub-populations. Under a gradual increase of the total load, the rupture of a heterogeneous adhesion cluster can be thought of as a multistep discrete process, in which one of the bond sub-populations ruptures first, followed by similar rupture steps of other sub-populations or by immediate detachment of the remaining cluster. This rupture behavior is qualitatively independent of involved bond types, such as slip and catch bonds. Interestingly, an optimal stability is generally achieved when the total cluster load is shared such that loads on distinct bond populations are equal to their individual critical rupture forces. We also show that cluster heterogeneity can drastically affect cluster lifetime.

physics.bio-ph↗

Competing effects of inertia, sheet elasticity, and fluid viscoelasticity on the synchronization of two actuated sheets

Synchronization of two actuated sheets serves as a simple model for the interaction between flagellated microswimmers. Various factors, including inertia, sheet elasticity, and fluid viscoelasticity, have been suggested to facilitate the synchronization of two sheets; however, the importance of different contributions to this process still remains unclear. We perform a systematic investigation of competing effects of inertia, sheet elasticity, and fluid viscoelasticity on the synchronization of two sheets. Characteristic time $τ^\mathrm{s}$ for the synchronization caused by inertial effects is inversely proportional to sheet Reynolds number $\mathrm{Re}$, such that $τ^\mathrm{s} ω\propto \mathrm{Re}^{-1}$ with $ω$ being the wave frequency. Synchronization toward stable in-phase or opposite-phase configuration of two sheets is determined by the competition of inertial effects, sheet elasticity, fluid compressibility and viscoelasticity. Interestingly, fluid viscoelasticity results in strong synchronization forces for large beating amplitudes and Deborah numbers $\mathrm{De} > 1$, which dominates over other factors and favors the in-phase configuration. Therefore, our results show that fluid viscoelasticity can dramatically enhance synchronization of microswimmers. Our investigation deciphers the importance of different competing effects for the synchronization of two actuated sheets, leading to a better understanding of interactions between microswimmers and their collective behavior.

physics.flu-dyn↗

Effect of cytosol viscosity on the flow behavior of red blood cell suspensions in microvessels

The flow behavior of blood in microvessels is directly associated with tissue perfusion and oxygen delivery. Current efforts on modeling blood flow have primarily focused on the flow properties of blood with red blood cells (RBCs) having a viscosity ratio $C$ of unity between the cytosol and suspending medium, while under physiological conditions the cytosol viscosity is about five times larger than the plasma viscosity (i.e., $C\approx 5$). The importance of $C$ for the behavior of single RBCs in fluid flow has already been demonstrated, while the effect of $C$ on blood flow has only been sparsely studied. We employ mesoscopic hydrodynamic simulations to perform a systematic investigation of flow properties of RBC suspensions with different cytosol viscosities for various flow conditions in cylindrical microchannels. Our main aim is to link macroscopic flow properties such as flow resistance to single cell deformation and dynamics as a function of $C$. Starting from a dispersed cell configuration, we find that the flow convergence and the development of a RBC-free layer (RBC-FL) depend only weakly on $C$, and require a convergence length in the range of $25D-50D$, where $D$ is the channel diameter. The flow resistance for $C=5$ is nearly the same as that for $C=1$, which is facilitated by a slightly larger RBC-FL thickness for $C=5$. This effect is due to the suppression of membrane motion and dynamic shape deformations by a more viscous cytosol for $C=5$, resulting in a more compact cellular core of the flow in comparison to $C=1$. The weak effect of cytosol viscosity on the flow resistance and RBC-FL explains why cells can have a high concentration of hemoglobin for efficient oxygen delivery, without a pronounced increase in the flow resistance.

cond-mat.soft↗

Sculpting vesicles with active particles: Less is more

Biological cells are able to generate intricate structures and respond to external stimuli, sculpting their membrane from within. Simplified biomimetic systems can aid in understanding the principles which govern these shape changes and elucidate the response of the cell membrane under strong deformations. Here, a combined experimental and simulation approach is used to identify the conditions under which different non-equilibrium shapes and distinct active shape fluctuations can be obtained by enclosing self-propelled particles in giant vesicles. Interestingly, the most pronounced shape changes are observed at relatively low particle loadings, starting with the formation of tether-like protrusions to highly branched, dendritic structures. At high volume fractions, globally deformed vesicle shapes are observed. The obtained state diagram of vesicles sculpted by active particles predicts the conditions under which local internal forces can generate dramatic cell shape changes, such as branched structures in neurons.

cond-mat.soft↗

Dissipative particle dynamics with energy conservation: isoenergetic integration and transport properties

Simulations of nano- to micro-meter scale fluidic systems under thermal gradients require consistent mesoscopic methods accounting for both hydrodynamic interactions and proper transport of energy. One such method is dissipative particle dynamics with energy conservation (DPDE), which has been used for various fluid systems with non-uniform temperature distributions. Despite the success of the method, existing integration algorithms have shown to result in an undesired energy drift, putting into question whether the DPDE method properly captures properties of real fluids. We propose a modification of the velocity-Verlet algorithm with local energy conservation for each DPDE particle, such that the total energy is conserved up to machine precision. Furthermore, transport properties of a DPDE fluid are analyzed in detail. In particular, an analytical approximation for the thermal conductivity coefficient is derived, which allows the selection of a specific value a priori. Finally, we provide approximate expressions for the dimensionless Prandtl and Schmidt numbers, which characterize fluid transport properties and can be adjusted independently by a proper selection of model parameters, and therefore, made comparable with those of real fluids. In conclusion, our results strengthen the DPDE method as a very robust approach for the investigation of mesoscopic systems with temperature inhomogeneities.

cond-mat.soft↗

Deformation and dynamics of erythrocytes govern their traversal through microfluidic devices with a deterministic lateral displacement architecture

Deterministic lateral displacement (DLD) microfluidic devices promise versatile and precise processing of biological samples. However, this prospect has been realized so far only for rigid spherical particles and remains limited for biological cells due to the complexity of cell dynamics and deformation in microfluidic flow. We employ mesoscopic hydrodynamics simulations of red blood cells (RBC) in DLD devices with circular posts to better understand the interplay between cell behavior in complex microfluidic flow and sorting capabilities of such devices. We construct a mode diagram of RBC behavior (e.g. displacement, zig-zagging, and intermediate modes) and identify several regimes of RBC dynamics (e.g. tumbling, tank-treading, and trilobe motion). Furthermore, we link the complex interaction dynamics of RBCs with the post to their effective cell size and discuss relevant physical mechanisms governing the dynamic cell states. In conclusion, sorting of RBCs in DLD devices based on their shear elasticity is in general possible, but requires fine-tuning of flow conditions to targeted mechanical properties of the RBCs.

cond-mat.soft↗

Sharp-edged geometric obstacles in microfluidics promote deformability-based sorting of cells

Sorting cells based on their intrinsic properties is a highly desirable objective, since changes in cell deformability are often associated with various stress conditions and diseases. Deterministic lateral displacement (DLD) devices offer high precision for rigid spherical particles, while their success in sorting deformable particles remains limited due to the complexity of cell traversal in DLDs. We employ mesoscopic hydrodynamics simulations and demonstrate prominent advantages of sharp-edged DLD obstacles for probing deformability properties of red blood cells (RBCs). By consecutive sharpening of the pillar shape from circular to diamond to triangular geometry, a pronounced cell bending around an edge is achieved, serving as a deformability sensor. Bending around the edge is the primary mechanism, which governs the traversal of RBCs through such DLD device. This strategy requires an appropriate degree of cell bending by fluid stresses, which can be controlled by the flow rate, and exhibits good sensitivity to moderate changes in cell deformability. We expect that similar mechanisms should be applicable for the development of novel DLD devices that target intrinsic properties of many other cells.

physics.flu-dyn↗

Sorting of particles suspended in whole blood

An important step in diagnostics is the isolation of specific cells and microorganisms of interest from blood. Since such bioparticles are often present at very low concentrations, throughput needs to be as high as possible. In addition, to ensure simplicity, a minimum of sample preparation is important. Therefore, sorting schemes that function for whole blood are highly desirable. Deterministic lateral displacement (DLD) has proven to be very precise and versatile in terms of a wide range of sorting parameters. To better understand how DLD performs for blood as the hematocrit increases, we have performed measurements and simulations for spherical particles in the micrometer range moving through DLD arrays for different flow velocities and hematocrits ranging from pure buffer to whole blood. We find that the separation function of the DLD array is sustained, even though blood cells introduce a shift in the trajectories and a significant dispersion for particles that are close to the critical size in the device. Simulations qualitatively replicate our experimental observations and help us identify fundamental mechanisms for the effect of hematocrit on the performance of the DLD device.

cond-mat.soft↗

A new look at blood shear-thinning

Blood viscosity decreases with shear stress, a property essential for an efficient perfusion of the vascular tree. Shear-thinning is intimately related to the dynamics and mutual interactions of red blood cells (RBCs), the major constituents of blood. Our work explores RBCs dynamics under physiologically relevant conditions of flow strength, outer fluid viscosity and volume fraction. Our results contradict the current paradigm stating that RBCs should align and elongate in the flow direction thanks to their membrane circulation around their center of mass, reducing flow-lines disturbances. On the contrary, we observe both experimentally and with simulations, rich morphological transitions that relate to global blood rheology. For increasing shear stresses, RBCs successively tumble, roll, deform into rolling stomatocytes and finally adopt highly deformed and polylobed shapes even for semi-dilute volume fractions analogous to microcirculatory values. Our study suggests that any pathological change in plasma composition, RBCs cytosol viscosity or membrane mechanical properties will impact the onset of shape transitions and should play a central role in pathological blood rheology and flow behavior.

physics.bio-ph↗