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Amir Khosravanizadeh

Publications and source records attributed to Amir Khosravanizadeh.

6 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↗

Mechanical properties of chiral actin filaments

The mechanical properties of actin filaments are essential to their biological functions. Here, we introduce a highly coarse-grained model of actin filaments that preserves helicity and chirality while enabling mesoscale simulations. The framework is implemented in Cytosim, an open-source cytoskeleton simulation platform. We can predict and finely control the shape and mechanical properties of this helical filament, that can be matched to experimental values. Using this model, we investigated the role of filament chirality in motor-driven dynamics. We first show that in two different experimental configurations, motor movement along a helical filament results in a chiral motion of the filament. In a bundle of helical filaments, dimeric motors exert torques on each filament, inducing collective behaviors in the bundle such as rotation, coiling, and helical buckling, reminiscent of those observed in filopodia. Together, these results demonstrate the central role of helicity and chirality in actin mechanics and motor-driven dynamics, and establish our framework as a powerful tool for mesoscale simulations. This framework can also be used for other helical filaments beyond actin.

physics.bio-ph↗

Rotation-Beating dynamics of a driven flexible filament: role of motor protein properties

We have used numerical simulations to investigate how the properties of motor proteins control the dynamical behavior of a driven flexible filament. The filament is pinned at one end and positioned on top of a patch of anchored motor proteins, a setup commonly referred to as a spiral gliding assay. In nature, there is a variety of motor proteins with different properties. In this study, we have investigated the role of detachment rate, detachment force, stall force, and unloaded speed of motors on the dynamical behavior of the filament. We found that this system generally can show three different regimes: 1) Fluctuation, where the filament undergoes random fluctuations because the motors are unable to bend it. 2) Rotation, in which the filament bends and then moves continuously in one direction. 3) Beating, where the filament's direction of rotation changes over time. We found that the transition between fluctuation and rotation occurs when motors exert a force sufficient to buckle the filament. The threshold force coincides to the second buckling mode of a filament undergoing a continuously distributed load. Moreover, we showed that when motors near the pining point work close to their stall force, they get stuck and act as a second pin, leading to the beating regime.

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↗

Wrinkling instability in 3D active nematics

In nature interactions between biopolymers and motor proteins give rise to biologically essential emergent behaviours. Besides cytoskeleton mechanics, active nematics arise from such interactions. Here we present a study on 3D active nematics made of microtubules, kinesin motors and depleting agent. It shows a rich behaviour evolving from a nematically ordered space-filling distribution of microtubule bundles toward a flattened and contracted 2D ribbon that undergoes a wrinkling instability and subsequently transitions into a 3D active turbulent state. The wrinkle wavelength is independent of the ATP concentration and our theoretical model describes its relation with the appearance time. We compare the experimental results with a numerical simulation that confirms the key role of kinesin motors in cross-linking and sliding the microtubules. Our results on the active contraction of the network and the independence of wrinkle wavelength on ATP concentration are important steps forward for the understanding of these 3D systems.

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↗