Biology subjects

Gompper, G.

Publications and source records attributed to Gompper, G..

13 recordsLinked to original sources

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↗

bioRxiv2024

Adhesion-driven vesicle translocation through membrane-covered pores

Translocation across barriers and through constrictions is a mechanism that is often used in vivo for transporting material between compartments. A specific example is apicomplexan parasites invading host cells through the tight junction that acts as a pore, and a similar barrier crossing is involved in drug delivery using lipid vesicles on the skin. Here, we use triangulated membranes and energy minimization to study the translocation of vesicles through pores with fixed radii. The vesicles bind to a lipid bilayer spanning the pore, and the adhesion-energy gain drives the translocation; the vesicle deformation while squeezing through leads to an energy barrier. In addition, the deformation-energy cost for deforming the pore-spanning membrane hinders translocation. Increasing the bending rigidity of the pore-spanning membrane and decreasing the pore size both increase the barrier height and shift the maximum to smaller translocation fractions. We compare the translocation of initially spherical vesicles with fixed membrane area and freely adjustable volume to that of initially prolate vesicles with fixed membrane area and volume. In the latter case, translocation can be entirely suppressed. Our predictions may help rationalize the invasion of apicomplexan parasites into host cells and design measures to combat the diseases they transmit.

biophysics↗

bioRxiv2023

Type-IV pili tune an adhesion-migration trade-off during surface colonization of Pseudomonas aeruginosa

Bacterial pathogenicity relies on both firm surface adhesion and cell dissemination. How twitching bacteria resolve the fundamental contradiction between adhesion and migration is unknown. To address this question, we employ live-cell imaging of type-IV pili (T4P) and therewith construct a comprehensive mathematical model of Pseudomonas aeruginosa migration. The data show that only 10% to 50% of T4P bind to substrates and contribute to migration through random extension and retraction. Individual T4P do not display a measurable sensory response to surfaces, but their number increases on cellular surface contact. Attachment to surfaces is mediated, besides T4P, by passive adhesive forces acting on the cell body. Passive adhesions slow down cell migration and result in local random motion on short time scales, which is followed by directionally persistent, superdiffusive motion on longer time scales. Moreover, passive adhesions strongly enhance surface attachment under shear flow. {Delta}pilA mutants, which produce no T4P, robustly stick to surfaces under shear flow. In contrast, rapidly migrating {Delta}pilH cells, which produce an excessive number of T4P, are easily detached by shear. Wild-type cells sacrifice migration speed for robust surface attachment by maintaining a low number of active pili. The different cell strains pertain to disjunct regimes in a generic adhesion-migration trait space. Depending on the nature of the adhesion structures, adhesion and migration are either compatible or a trade-off is required for efficient bacterial surface colonization under different conditions.

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↗

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

The role of thickness inhomogeneities in hierarchical cortical folding

The morphology of the mammalian brain cortex is highly folded. For long it has been known that specific patterns of folding are necessary for an optimally functioning brain. On the extremes, lissencephaly, a lack of folds in humans, and polymicrogyria, an overly folded brain, can lead to severe mental retardation, short life expectancy, epileptic seizures, and tetraplegia. The construction of a quantitative model on how and why these folds appear during the development of the brain is the first step in understanding the cause of these conditions. In recent years, there have been various attempts to understand and model the mechanisms of brain folding. Previous works have shown that mechanical instabilities play a crucial role in the formation of brain folds, and that the geometry of the fetal brain is one of the main factors in dictating the folding characteristics. However, modeling higher-order folding, one of the main characteristics of the highly gyrencephalic brain, has not been fully tackled. The effects of thickness inhomogeneity in the gyrogenesis of the mammalian brain are studied in silico. Finite-element simulations of rectangular slabs are performed. The slabs are divided into two distinct regions, where the outer layer mimics the gray matter, and the inner layer the underlying white matter. Differential growth is introduced by growing the top layer tangentially, while keeping the underlying layer untouched. The brain tissue is modeled as a neo-Hookean hyperelastic material. Simulations are performed with both, homogeneous and inhomogeneous cortical thickness. The homogeneous cortex is shown to fold into a single wavelength, as is common for bilayered materials, while the inhomogeneous cortex folds into more complex conformations. In the early stages of development of the inhomogeneous cortex, structures reminiscent of the deep sulci in the brain are obtained. As the cortex continues to develop, secondary undulations, which are shallower and more variable than the structures obtained in earlier gyrification stage emerge, reproducing well-known characteristics of higher-order folding in the mammalian, and particularly the human, brain.

neuroscience↗

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

Tissue evolution: Mechanical interplay of adhesion, pressure, and heterogeneity

The evolution of various competing cell types in tissues, and the resulting persistent tissue population, is studied numerically and analytically in a particle-based model of active tissues. Mutations change the properties of cells in various ways, including their mechanical properties. Each mutation results in an advantage or disadvantage to grow in the competition between different cell types. While changes in signaling processes and biochemistry play an important role, we focus on changes in the mechanical properties by studying the result of variation of growth force and adhesive cross-interactions between cell types. For independent mutations of growth force and adhesion strength, the tissue evolves towards cell types with high growth force and low internal adhesion strength, as both increase the homeostatic pressure. Motivated by biological evidence, we postulate a coupling between both parameters, such that an increased growth force comes at the cost of a higher internal adhesion strength or vice versa. This tradeoff controls the evolution of the tissue, ranging from unidirectional evolution to very heterogeneous and dynamic populations. The special case of two competing cell types reveals three distinct parameter regimes: Two in which one cell type outcompetes the other, and one in which both cell types coexist in a highly mixed state. Interestingly, a single mutated cell alone suffices to reach the mixed state, while a finite mutation rate affects the results only weakly. Finally, the coupling between changes in growth force and adhesion strength reveals a mechanical explanation for the evolution towards intra-tumor heterogeneity, in which multiple species coexist even under a constant evolutianary pressure.\n\nAuthor summaryThe evolution of cell populations in growing tissues is due to mutations during cell division, and subsequent competition through various biochemical and mechanical factors. Cancer represents an example of such an evolution on a short time scale. It is a multistep process, where several mutations are needed in order for a tumor to develop and become malignant. Furthermore, cell types in a tumor are often found to be very heterogeneous. We employ computer simulations of a particle-based model of growing tissues to study the competition of various cell types through variations of the mechanical cell properties. Unconstraint evolution drives the tissue towards cell types with stronger growth force and reduced adhesion. However, growth force and adhesion are not independent. Motivated by biologcal evidence, we consider a tissue, where enhanced growth force is coupled to increased adhesion. In a regime around a balanced tradeoff, multiple cell types coexist in a tissue, providing a tentative explanation for tumor heterogeneity. The special case of a competition between two cell types facilitates the study of the underlying competition mechanism. For example, we find that the number fraction of mutated cells is nearly independent of the mutation rate km, as long as km is much smaller than the apoptosis rate ka.

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↗

bioRxiv2019

Substrate-rigidity dependent migration of an idealized twitching bacterium

Mechanical properties of the extracellular matrix are important determinants of cellular migration in diverse processes, such as immune response, wound healing, and cancer metastasis. Moreover, recent studies indicate that even bacterial surface colonization can depend on the mechanics of the substrate. Here, we focus on physical mechanisms that can give rise to substrate-rigidity dependent migration. We study a \"twitcher\", a cell driven by extension-retraction cycles, to idealize bacteria and perhaps eukaryotic cells that employ a slip-stick mode of motion. The twitcher is asymmetric and always pulls itself forward at its front. Analytical calculations show that the migration speed of a twitcher depends non-linearly on substrate rigidity. For soft substrates, deformations do not lead to build-up of significant force and the migration speed is therefore determined by stochastic adhesion unbinding. For rigid substrates, forced adhesion rupture determines the migration speed. Depending on the force-sensitivity of front and rear adhesions, forced bond rupture implies an increase or a decrease of the migration speed. A requirement for the occurrence of rigidity-dependent stick-slip migration is a \"sticky\" substrate, with binding rates being an order of magnitude larger than unbinding rates in absence of force. Computer simulations show that small stall forces of the driving machinery lead to a reduced movement on high rigidities, regardless of force-sensitivities of bonds. The simulations also confirm the occurrence of rigidity-dependent migration speed in a generic model for slip-stick migration of cells.

biophysics↗

bioRxiv2018

Chronology of motor-mediated microtubule streaming

We introduce a computer-based simulation model for coarse-grained, effective motor-mediated interaction between microtubule pairs to study the time-scales that compose cytoplasmic streaming. We characterise microtubule dynamics in two-dimensional systems by chronologically arranging five distinct processes of varying duration that make up streaming, from microtubule pairs to collective dynamics. The structures found were polarity sorted due to the propulsion of antialigned microtubules. This also gave rise to the formation of large polar-aligned domains, and streaming at the domain boundaries. Correlation functions, mean squared displacements, and velocity distributions reveal a cascade of processes ultimately leading to microtubule streaming and advection, spanning multiple microtubule lengths. The characteristic times for the processes span over three orders of magnitude from fast single-microtubule processes to slow collective processes. Our approach can be used to directly test the importance of molecular components, such as motors and crosslinking proteins between microtubules, on the collective dynamics at cellular scale.

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↗