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 penetrating intact skin. Here, we use triangulated membranes and energy minimization to study the translocation of vesicles through pores with fixed radii.

The role of flow in the self-assembly of dragline spider silk proteins.

Hydrodynamic flow in the spider duct induces conformational changes in dragline spider silk proteins (spidroins) and drives their assembly, but the underlying physical mechanisms are still elusive. Here we address this challenging multiscale problem with a complementary strategy of atomistic and coarse-grained molecular dynamics simulations with uniform flow. The conformational changes at the molecular level were analyzed for single-tethered spider silk peptides.

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 particle gel rather than with the sedimentation of disjoint aggregates.

Erythrocyte Sedimentation: Collapse of a High-Volume-Fraction Soft-Particle Gel.

The erythrocyte sedimentation rate is one of the oldest medical diagnostic methods whose physical mechanisms remain debatable today. Using both light microscopy and mesoscale cell-level simulations, we show that erythrocytes form a soft-particle gel. Furthermore, the high volume fraction of erythrocytes, their deformability, and weak attraction lead to unusual properties of this gel.

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 parasite's apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically unfavorable process.

Functionalized supported membranes for quantifying adhesion of P. falciparum-infected erythrocytes.

The pathology of Plasmodium falciparum malaria is largely defined by the cytoadhesion of infected erythrocytes to the microvascular endothelial lining. The complexity of the endothelial surface and the large range of interactions available for the infected erythrocyte via parasite-encoded adhesins make analysis of critical contributions during cytoadherence challenging to define. Here, we have explored supported membranes functionalized with two important adhesion receptors, ICAM1 or CD36, as a quantitative biomimetic surface to help understand the processes involved in cytoadherence.

The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib.

Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified.

Acanthocyte Sedimentation Rate as a Diagnostic Biomarker for Neuroacanthocytosis Syndromes: Experimental Evidence and Physical Justification.

(1) Background: Chorea-acanthocytosis and McLeod syndrome are the core diseases among the group of rare neurodegenerative disorders called neuroacanthocytosis syndromes (NASs). NAS patients have a variable number of irregularly spiky erythrocytes, so-called acanthocytes. Their detection is a crucial but error-prone parameter in the diagnosis of NASs, often leading to misdiagnoses.

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.

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. To invade red blood cells (RBCs), apicomplexan parasites have to adhere with their apex to the RBC membrane. This necessary apex-membrane contact (or alignment) is not immediately established because the orientation of a free merozoite with respect to the RBC membrane is random when an adhesion contact first occurs.

State diagram for wall adhesion of red blood cells in shear flow: from crawling to flipping.

Red blood cells in shear flow show a variety of different shapes due to the complex interplay between hydrodynamics and membrane elasticity. Malaria-infected red blood cells become generally adhesive and less deformable. Adhesion to a substrate leads to a reduction in shape variability and to a flipping motion of the non-spherical shapes during the mid-stage of infection.

The sickle cell trait affects contact dynamics and endothelial cell activation in -infected erythrocytes.

Sickle cell trait, a common hereditary blood disorder, protects carriers from severe disease in infections with the human malaria parasite . Protection is associated with a reduced capacity of parasitized erythrocytes to cytoadhere to the microvascular endothelium and cause vaso-occlusive events. However, the underpinning cellular and biomechanical processes are only partly understood and the impact on endothelial cell activation is unclear.

Adhesion-based sorting of blood cells: an adhesive dynamics simulation study.

Blood cells can be sorted in microfluidic devices not only based on their sizes and deformability, but also based on their adhesive properties. In particular, white blood cells have been shown to be sorted out by using adhesive micropatterns made from stripes that are tilted in regard to the direction of shear flow. Here we use adhesive dynamics simulations for round cells to quantitatively investigate this effect and to predict the optimal tilt angle.

Rolling Adhesion of Schizont Stage Malaria-Infected Red Blood Cells in Shear Flow.

To avoid clearance by the spleen, red blood cells infected with the human malaria parasite Plasmodium falciparum (iRBCs) adhere to the vascular endothelium through adhesive protrusions called "knobs" that the parasite induces on the surface of the host cell. However, the detailed relation between the developing knob structure and the resulting movement in shear flow is not known. Using flow chamber experiments on endothelial monolayers and tracking of the parasite inside the infected host cell, we find that trophozoites (intermediate-stage iRBCs) tend to flip due to their biconcave shape, whereas schizonts (late-stage iRBCs) tend to roll due to their almost spherical shape.

Differential time-dependent volumetric and surface area changes and delayed induction of new permeation pathways in P. falciparum-infected hemoglobinopathic erythrocytes.

During intraerythrocytic development, Plasmodium falciparum increases the ion permeability of the erythrocyte plasma membrane to an extent that jeopardizes the osmotic stability of the host cell. A previously formulated numeric model has suggested that the parasite prevents premature rupture of the host cell by consuming hemoglobin (Hb) in excess of its own anabolic needs. Here, we have tested the colloid-osmotic model on the grounds of time-resolved experimental measurements on cell surface area and volume.

Modeling cytoadhesion of Plasmodium falciparum-infected erythrocytes and leukocytes-common principles and distinctive features.

Cytoadhesion of Plasmodium falciparum-infected erythrocytes to the microvascular endothelial lining shares striking similarities to cytoadhesion of leukocytes. In both cases, adhesins are presented in structures that raise them above the cell surface. Another similarity is the enhancement of adhesion under physical force (catch bonding).

Slow closure of denaturation bubbles in DNA: twist matters.

The closure of long equilibrated denaturation bubbles in DNA is studied using Brownian dynamics simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring freely rotating strands, with a nonzero torsional modulus in the duplex state, κ(φ)=200 to 300k(B)T. For DNAs of lengths N=40 to 100 base pairs (bps) with a large initial bubble in their middle, long closure times of 0.

Multifractal analysis of HIV-1 genomes.

Pathogens like HIV-1, which evolve into many closely related variants displaying differential infectivity and evolutionary dynamics in a short time scale, require fast and accurate classification. Conventional whole genome sequence alignment-based methods are computationally expensive and involve complex analysis. Alignment-free methodologies are increasingly being used to effectively differentiate genomic variations between viral species.