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Farshid Mohammad-Rafiee

Publications and source records attributed to Farshid Mohammad-Rafiee.

14 recordsLinked to original sources

Cellular wrapping of elastic particles by a supported lipid membrane

Constancy of life vitally depends on the internalization of particles through biomembranes. Of particular interest, cellular uptake, including phagocytosis, receptor-mediated endocytosis, and membrane fusion, critically depends on the elasticity of particles. Cellular membranes are strongly linked to a supporting cytoskeleton. However, in most previous studies, the effect of this cortical network somehow is overlooked. In this paper, we study the cellular wrapping of a membrane around a 2D elastic particle in the presence of a substrate mimicking cytoskeleton. Our simulations show that the impact of particle flexibility on the wrapping process depends on the magnitude of the membrane particle adhesion. In contrast, the extent of membrane protrusions formed around the target always increases with target stiffness. Since the extension of membrane protrusions is an essential step in the phagocytosis process, this result may indicate a selective behavior of macrophages in the phagocytosis of aged red blood cells.

cond-mat.soft

Role of particle local curvature in cellular wrapping

Cellular uptake through the lipid membranes plays an important role in adsorbing nutrients and fighting infection and can be used for drug delivery and nanomedicine developments. Endocytosis is one of the known pathways of the cellular uptake which associate with elastic deformation of the membrane wrapping around the foreign particle. The deformability of the membrane itself is strongly regulated by the presence of a cortical cytoskeleton placed underneath the membrane. It has been shown that size, shape, and orientation of the particles influence on their entry into the cell. Here, we study the role of particle local curvature in the cellular uptake by investigating the wrapping of an elastic membrane around a long cylindrical object with an elliptical cross section. The membrane itself is adhered to a substrate mimicking the cytoskeleton. Membrane wrapping proceeds differently whether the initial contact occurs at the particle's highly curved tip (prolate) or along its long side (oblate). We obtain a wrapping phase diagram as a function of the membrane-cytoskeleton and the membrane-target adhesion energy, which includes three distinct regimes of engulfment(unwrapped, partially wrapped, and fully wrapped), separated by two phase transitions. We also provide analytical expressions for the boundary between the different regimes which confirm that the transitions strongly depend on the orientation and aspect ratio of the particle.

cond-mat.soft

Receptor-Mediated Endocytosis of a Cylindrical Nanoparticle in the Presence of Cytoskeleton Substrate

Internalization of particles by cells plays a crucial role for adsorbing nutrients and fighting infection. Endocytosis is one of the most important mechanisms of the particles uptake which encompass multiple pathways. Although endocytosis is a complex mechanism involving biochemical signaling and active force generation, the energetic cost associated to the large deformations of the cell membrane wrapping around the foreign particle is an important factor controlling this process, which can be studied using quantitative physical models. Of particular interest is the competition between membrane - cytoskeleton and membrane - target adhesion. Here, we explore the wrapping of a lipid membrane around a long cylindrical object in the presence of a substrate mimicking the cytoskeleton. Using discretization of the Helfrich elastic energy that accounts for the membrane bending rigidity and surface tension, we obtain a wrapping phase diagram as a function of the membrane-cytoskeleton and the membrane-target adhesion energy that includes unwrapped, partially wrapped and fully wrapped states. We provide an analytical expression for the boundary between the different regimes. While the transition to partial wrapping is independent of membrane tension, the transition to full wrapping is very much influenced by membrane tension. We also show that target wrapping may proceed in an asymmetric fashion in the full wrapping regime.

cond-mat.soft

Modelling of Dictyostelium Discoideum Movement in Linear Gradient of Chemoattractant

Chemotaxis is a ubiquitous biological phenomenon in which cells detect a spatial gradient of chemoattractant, and then move towards the source. Here we present a position-dependent advection-diffusion model that quantitatively describes the statistical features of the chemotactic motion of the social amoeba {\it Dictyostelium discoideum} in a linear gradient of cAMP (cyclic adenosine monophosphate). We fit the model to experimental trajectories that are recorded in a microfluidic setup with stationary cAMP gradients and extract the diffusion and drift coefficients in the gradient direction. Our analysis shows that for the majority of gradients, both coefficients decrease in time and become negative as the cells crawl up the gradient. The extracted model parameters also show that besides the expected drift in the direction of chemoattractant gradient, we observe a nonlinear dependency of the corresponding variance in time, which can be explained by the model. Furthermore, the results of the model show that the non-linear term in the mean squared displacement of the cell trajectories can dominate the linear term on large time scales.

physics.bio-ph

Modeling of Ribosome Dynamics on a ds-mRNA under an External Load

Protein molecules in cells are synthesized by macromolecular machines called ribosomes. According to recent experimental data, we reduce the complexity of the ribosome and propose a model to express its activity in six main states. Using our model, we study the translation rate in different biological relevant situations in the presence of external force, and translation through the RNA double stranded region in the absence or presence of the external force. In the present study, we give a quantitative theory for translation rate and show that the ribosome behaves more like a Brownian Ratchet motor. Our findings could shed some light on understanding behaviors of the ribosome in biological conditions.

q-bio.SC

Elastic Model for Dinucleosome Structure and Energy

The equilibrium structure of a Dinucleosome is studied using an elastic model that takes into account the force and torque balance conditions. Using the proper boundary conditions, it is found that the conformational energy of the problem does not depend on the length of the linker DNA. In addition it is shown that the two histone octamers are almost perpendicular to each other and the linker DNA in short lengths is almost straight. These findings could shed some light on the role of DNA elasticity in the chromatin structure.

physics.bio-ph

Distribution of counterions and interaction between two similarly charged dielectric slabs: Roles of charge discreteness and dielectric inhomogeneity

The distribution of counterions and the electrostatic interaction between two similarly charged dielectric slabs is studied in the strong coupling limit. Dielectric inhomogeneities and discreteness of charge on the slabs have been taken into account. It is found that the amount of dielectric constant difference between the slabs and the environment, and the discreteness of charge on the slabs have opposing effects on the equilibrium distribution of the counterions. At small inter-slab separations, increasing the amount of dielectric constant difference increases the tendency of the counterions toward the middle of the intersurface space between the slabs and the discreteness of charge pushes them to the surfaces of the slabs. In the limit of point charges, independent of the strength of dielectric inhomogeneity, counterions distribute near the surfaces of the slabs. The interaction between the slabs is attractive at low temperatures and its strength increases with the dielectric constant difference. At room temperature, the slabs may completely attract each other, reach to an equilibrium separation or have two equilibrium separations with a barrier in between, depending on the system parameters.

physics.bio-ph

Effect of Bending Anisotropy on the 3D Conformation of Short DNA Loops

The equilibrium three dimensional shape of relatively short loops of DNA is studied using an elastic model that takes into account anisotropy in bending rigidities. Using a reasonable estimate for the anisotropy, it is found that cyclized DNA with lengths that are not integer multiples of the pitch take on nontrivial shapes that involve bending out of planes and formation of kinks. The effect of sequence inhomogeneity on the shape of DNA is addressed, and shown to enhance the geometrical features. These findings could shed some light on the role of DNA conformation in protein--DNA interactions.

q-bio.BM

Stochastic model for nucleosome sliding in the presence of DNA ligands

Heat-induced mobility of nucleosomes along DNA is an experimentally well-studied phenomenon. A recent experiment shows that the repositioning is modified in the presence of minor-groove binding DNA ligands. We present here a stochastic three-state model for the diffusion of a nucleosome along DNA in the presence of such ligands. It allows us to describe the dynamics and the steady state of such a motion analytically. The analytical results are in excellent agreement with numerical simulations of this stochastic process.With this model, we study the response of a nucleosome to an external force and how it is affected by the presence of ligands.

cond-mat.soft

On the effective charge of hydrophobic polyelectrolytes

In this paper we analyze the behavior of hydrophobic polyelectrolytes. It has been proposed that this system adopts a pearl-necklace structure reminiscent of the Rayleigh instability of a charged droplet. Using a Poisson-Boltzmann approach, we calculate the counterion distribution around a given pearl assuming the latter to be penetrable for the counterions. This allows us to calculate the effective electric charge of the pearl as a function of the chemical charge. Our predictions are in very good agreement with the recent experimental measurements of the effective charge by Essafi et al. (Europhys. Lett. 71, 938 (2005)). Our results allow to understand the large deviation from the Manning law observed in these experiments.

cond-mat.soft

Elastic Correlations in Nucleosomal DNA Structure

The structure of DNA in the nucleosome core particle is studied using an elastic model that incorporates anisotropy in the bending energetics and twist-bend coupling. Using the experimentally determined structure of nucleosomal DNA [T.J. Richmond and C.A. Davey, Nature {\bf 423}, 145 (2003)], it is shown that elastic correlations exist between twist, roll, tilt, and stretching of DNA, as well as the distance between phosphate groups. The twist-bend coupling term is shown to be able to capture these correlations to a large extent, and a fit to the experimental data yields a new estimate of G=25 nm for the value of the twist-bend coupling constant.

q-bio.BM

Theory of Nucleosome Corkscrew Sliding in the Presence of Synthetic DNA Ligands

Histone octamers show a heat-induced mobility along DNA. Recent theoretical studies have established two mechanisms that are qualitatively and quantitatively compatible with in vitro experiments on nucleosome sliding: Octamer repositiong through one-basepair twist defects and through ten-basepair bulge defects. A recent experiment demonstrated that the repositioning is strongly suppressed in the presence of minor-groove binding DNA ligands. In the present study we give a quantitative theory for nucleosome repositioning in the presence of such ligands. We show that the experimentally observed octamer mobilities are consistent with the picture of bound ligands blocking the passage of twist defects through the nucleosome. This strongly supports the model of twist defects inducing a corkscrew motion of the nucleosome as the underlying mechanism of nucleosome sliding. We provide a theoretical estimate of the nucleosomal mobility without adjustable parameters, as a function of ligand concentration, binding affinity, binding site orientiation, temperature and DNA anisotropy. Having this mobility at hand we speculate about the interaction between a nucleosome and a transcribing RNA polymerase and suggest a novel mechanism that might account for polymerase induced nucleosome repositioning.

q-bio.SC

Electrostatic Contribution to Twist Rigidity of DNA

The electrostatic contribution to twist rigidity of DNA is studied, and it is shown that the Coulomb self-energy of the double-helical sugar-phosphate backbone contributes considerably to twist rigidity of DNA--the electrostatic twist rigidity of DNA is found as $C_{\rm elec}\approx 5$ nm, which makes up about 7% of its total twist rigidity ($C_{\rm DNA}\approx 75$ nm). The electrostatic twist rigidity is found, however, to only weakly depend on the salt concentration, because of a competition between two different screening mechanisms: (1) Debye screening by the salt ions in the bulk, and (2) structural screening by the periodic charge distribution along the backbone of the helical polyelectrolyte. It is found that depending on the parameters, the electrostatic contribution could stabilize or destabilize the structure of a helical polyelectrolyte.

cond-mat.soft

Nonlinear Mechanical Response of DNA due to Anisotropic Bending Elasticity

The response of a short DNA segment to bending is studied, taking into account the anisotropy in the bending rigidities caused by the double-helical structure. It is shown that the anisotropy introduces an effective nonlinear twist-bend coupling that can lead to the formation of kinks and modulations in the curvature and/or in the twist, depending on the values of the elastic constants and the imposed deflection angle. The typical wavelength for the modulations, or the distance between the neighboring kinks is found to be set by half of the DNA pitch.

cond-mat.soft