scholarly journals Theoretical model of efficient phagocytosis driven by curved membrane proteins and active cytoskeleton forces

2022 ◽  
Author(s):  
Raj Kumar Sadhu ◽  
Sarah R. Barger ◽  
Samo Penic ◽  
Ales Iglic ◽  
Mira Krendel ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Energy Cost ◽  
Actin Polymerization ◽  
Three Dimensional ◽  
Leading Edge ◽  
Coarse Grained ◽  
Spherical Particles ◽  
Bending Energy ◽  
Protein Density ◽  
Curved Membrane

Phagocytosis is the process of engulfment and internalization of comparatively large particles by the cell, that plays a central role in the functioning of our immune system. We study the process of phagocytosis by considering a simplified coarse grained model of a three-dimensional vesicle, having uniform adhesion interaction with a rigid particle, in the presence of curved membrane proteins and active cytoskeletal forces. Complete engulfment is achieved when the bending energy cost of the vesicle is balanced by the gain in the adhesion energy. The presence of curved (convex) proteins reduces the bending energy cost by self-organizing with higher density at the highly curved leading edge of the engulfing membrane, which forms the circular rim of the phagocytic cup that wraps around the particle. This allows the engulfment to occur at much smaller adhesion strength. When the curved proteins exert outwards protrusive forces, representing actin polymerization, at the leading edge, we find that engulfment is achieved more quickly and at lower protein density. We consider spherical as well as non-spherical particles, and find that non-spherical particles are more difficult to engulf in comparison to the spherical particles of the same surface area. For non-spherical particles, the engulfment time crucially depends upon the initial orientation of the particles with respect to the vesicle. Our model offers a mechanism for the spontaneous self-organization of the actin cytoskeleton at the phagocytic cup, in good agreement with recent high-resolution experimental observations.

scholarly journals Effective mechanical potential of cell–cell interaction explains basic structures of three-dimensional morphogenesis

2019 ◽  
Author(s):  
Hiroshi Koyama ◽  
Hisashi Okumura ◽  
Atsushi M. Ito ◽  
Tetsuhisa Otani ◽  
Kazuyuki Nakamura ◽  
...  
Keyword(s):  
Mdck Cells ◽  
Three Dimensional ◽  
Cell Interaction ◽  
Fundamental Principle ◽  
Cell Interactions ◽  
Coarse Grained ◽  
Spherical Particles ◽  
Imaging Data ◽  
Effective Potentials ◽  
Cell Cell

AbstractMechanical properties of cell–cell interactions have been suggested to be critical for the emergence of diverse three-dimensional morphologies of multicellular organisms. Mechanical potential energy of cell–cell interactions has been theoretically assumed, however, whether such potential can be detectable in living systems remains poorly understood. In this study, we developed a novel framework for inferring mechanical forces of cell–cell interactions. First, by analogy to coarse-grained models in molecular and colloidal sciences, cells were approximately assumed to be spherical particles, where microscopic features of cells such as polarities and shapes were not explicitly incorporated and the mean forces (i.e. effective forces) of cell–cell interactions were considered. Then, the forces were statistically inferred from live imaging data, and subsequently, we successfully detected potentials of cell–cell interactions. Finally, computational simulations based on these potentials were performed to test whether these potentials can reproduce the original morphologies. Our results from various systems, including Madin-Darby canine kidney (MDCK) cells, C.elegans early embryos, and mouse blastocysts, suggest that the method can accurately infer the effective potentials and capture the diverse three-dimensional morphologies. Importantly, energy barriers were predicted to exist at the distant regions of the interactions, and this mechanical property of cell–cell interactions was essential for formation of cavities, tubes, cups, and two-dimensional sheets. Collectively, these structures constitute basic structures observed during morphogenesis and organogenesis. We propose that effective potentials of cell– cell interactions are parameters that can be measured from living organisms, and represent a fundamental principle underlying the emergence of diverse three-dimensional morphogenesis.

scholarly journals Modelling cellular spreading and emergence of motility in the presence of curved membrane proteins and active cytoskeleton forces

2021 ◽  
Author(s):  
Raj Kumar Sadhu ◽  
Samo Penič ◽  
Aleš Iglič ◽  
Nir S. Gov
Keyword(s):  
Membrane Proteins ◽  
Normal Development ◽  
Coarse Grained ◽  
High Concentration ◽  
Minimal Set ◽  
Coarse Grained Model ◽  
Flat Substrate ◽  
Substrate Adhesion ◽  
Energy Penalty ◽  
Curved Membrane

Eukaryotic cells adhere to extracellular matrix during the normal development of the organism, forming static adhesion as well as during cell motility. We study this process by considering a simplified coarse-grained model of a vesicle that has uniform adhesion energy with a flat substrate, mobile curved membrane proteins and active forces. We find that a high concentration of curved proteins alone increases the spreading of the vesicle, by the self-organization of the curved proteins at the high curvature vesicle-substrate contact line, thereby reducing the bending energy penalty at the vesicle rim. This is most significant in the regime of low bare vesicle-substrate adhesion. When these curved proteins induce protrusive forces, representing the actin cytoskeleton, we find efficient spreading, in the form of sheet-like lamellipodia. Finally, the same mechanism of spreading is found to include a minimal set of ingredients needed to give rise to motile phenotypes.

Simulation studies of the interactions between membrane proteins and detergents

2005 ◽  
Vol 33 (5) ◽  
pp. 910-912 ◽  
Author(s):  
P.J. Bond ◽  
J. Cuthbertson ◽  
M.S.P. Sansom
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Self Assembly ◽  
Kinetic Mechanism ◽  
Coarse Grained ◽  
Simulation Studies ◽  
High Resolution Data ◽  
Biologically Relevant ◽  
Structure And Dynamics ◽  
Detergent Interactions

Interactions between membrane proteins and detergents are important in biophysical and structural studies and are also biologically relevant in the context of folding and transport. Despite a paucity of high-resolution data on protein–detergent interactions, novel methods and increased computational power enable simulations to provide a means of understanding such interactions in detail. Simulations have been used to compare the effect of lipid or detergent on the structure and dynamics of membrane proteins. Moreover, some of the longest and most complex simulations to date have been used to observe the spontaneous formation of membrane protein–detergent micelles. Common mechanistic steps in the micelle self-assembly process were identified for both α-helical and β-barrel membrane proteins, and a simple kinetic mechanism was proposed. Recently, simplified (i.e. coarse-grained) models have been utilized to follow long timescale transitions in membrane protein–detergent assemblies.

scholarly journals Micromechanism of the Breakage of Two Spherical Gypsum Particles under Normal–Tangential Contact Conditions

2021 ◽  
Vol 11 (9) ◽  
pp. 4039
Author(s):  
Yiran Niu ◽  
Lin Li ◽  
Yanwei Zhang ◽  
Shicai Yu ◽  
Jian Zhou
Keyword(s):  
Tangential Force ◽  
Coarse Grained ◽  
Spherical Particles ◽  
Contact Conditions ◽  
Normal Contact ◽  
Tangential Contact ◽  
Theoretical Predictions ◽  
Tangential Forces ◽  
Predicted Values ◽  
The Relationship

Contact breakage of particles makes a large difference in the strength of coarse-grained soils, and exploring the characteristics within the process of the breakage is of great significance. Ignoring the influence of particle shape, the micromechanism of two spherical particles breaking under normal–tangential contact conditions was investigated theoretically and experimentally. Through theoretical analysis, the breakage form, the shape and size of the conical core, and the relationship between the normal and tangential forces at crushing were predicted. Particle contact tests of two gypsum spheres were carried out, in which the breakage forms, features of the conical cores and the normal and tangential forces at crushing were recorded for comparison with the predicted values. The test results and the theoretical predictions showed good agreement. Both the analysis and test demonstrate that the presence of tangential forces causes the conical core to assume the shape of an oblique cone, and the breakage form to change. Moreover, with increasing normal contact force, the tangential force needed for crushing increases gradually first and then decreases suddenly.

scholarly journals Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-Diseased Myometrium

2021 ◽  
Vol 22 (7) ◽  
pp. 3618
Author(s):  
Emmanuel N. Paul ◽  
Gregory W. Burns ◽  
Tyler J. Carpenter ◽  
Joshua A. Grey ◽  
Asgerally T. Fazleabas ◽  
...  
Keyword(s):  
Uterine Fibroid ◽  
Three Dimensional ◽  
Uterine Fibroids ◽  
Principal Component ◽  
Leading Edge ◽  
Gene Set Enrichment ◽  
Phenotypic Differences ◽  
False Discovery ◽  
Gene Sets ◽  
High Concordance

Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and compared them with fibroid (F) and matched myometrial (MF) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs. M were not found in the F vs. MF, which are likely understudied in the pathogenesis of uterine fibroids and could be key genes for future investigation. These results suggest that the transcriptome of fibroid-associated myometrium is different from that of non-diseased myometrium and that fibroid studies should consider using both matched myometrium and non-diseased myometrium as controls.

A Randomized Parallel Three-Dimensional Convex Hull Algorithm for Coarse-Grained Multicomputers

1997 ◽  
Vol 30 (6) ◽  
pp. 547-558 ◽  
Author(s):  
F. Dehne ◽  
X. Deng ◽  
P. Dymond ◽  
A. Fabri ◽  
A. A. Khokhar
Keyword(s):  
Convex Hull ◽  
Three Dimensional ◽  
Coarse Grained ◽  
Convex Hull Algorithm

Three-dimensional crystallization of membrane proteins

1988 ◽  
Vol 21 (4) ◽  
pp. 429-477 ◽  
Author(s):  
W. Kühlbrandt
Keyword(s):  
High Resolution ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Biological Macromolecules ◽  
X Ray ◽  
X Ray Crystallography ◽  
Membrane Protein Complexes ◽  
Essential Prerequisite

As recently as 10 years ago, the prospect of solving the structure of any membrane protein by X-ray crystallography seemed remote. Since then, the threedimensional (3-D) structures of two membrane protein complexes, the bacterial photosynthetic reaction centres of Rhodopseudomonas viridis (Deisenhofer et al. 1984, 1985) and of Rhodobacter sphaeroides (Allen et al. 1986, 1987 a, 6; Chang et al. 1986) have been determined at high resolution. This astonishing progress would not have been possible without the pioneering work of Michel and Garavito who first succeeded in growing 3-D crystals of the membrane proteins bacteriorhodopsin (Michel & Oesterhelt, 1980) and matrix porin (Garavito & Rosenbusch, 1980). X-ray crystallography is still the only routine method for determining the 3-D structures of biological macromolecules at high resolution and well-ordered 3-D crystals of sufficient size are the essential prerequisite.

Three-Dimensional and Rotational Aerodynamics on the NREL Phase VI Wind Turbine Blade

2008 ◽  
Vol 130 (3) ◽  
Author(s):  
Alvaro Gonzalez ◽  
Xabier Munduate
Keyword(s):  
Wind Turbine ◽  
Turbine Blade ◽  
Three Dimensional ◽  
Separated Flow ◽  
Leading Edge ◽  
Wind Turbine Blade ◽  
Trailing Edge ◽  
Rotating Blade ◽  
Nrel Phase Vi ◽  
Edge Separation

This work undertakes an aerodynamic analysis over the parked and the rotating NREL Phase VI wind turbine blade. The experimental sequences from NASA Ames wind tunnel selected for this study respond to the parked blade and the rotating configuration, both for the upwind, two-bladed wind turbine operating at nonyawed conditions. The objective is to bring some light into the nature of the flow field and especially the type of stall behavior observed when 2D aerofoil steady measurements are compared to the parked blade and the latter to the rotating one. From averaged pressure coefficients together with their standard deviation values, trailing and leading edge separated flow regions have been found, with the limitations of the repeatability of the flow encountered on the blade. Results for the parked blade show the progressive delay from tip to root of the trailing edge separation process, with respect to the 2D profile, and also reveal a local region of leading edge separated flow or bubble at the inner, 30% and 47% of the blade. For the rotating blade, results at inboard 30% and 47% stations show a dramatic suppression of the trailing edge separation, and the development of a leading edge separation structure connected with the extra lift.

scholarly journals Using kICS to Reveal Changed Membrane Diffusion of AQP-9 Treated with Drugs

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 568
Author(s):  
Jakob L. Kure ◽  
Thommie Karlsson ◽  
Camilla B. Andersen ◽  
B. Christoffer Lagerholm ◽  
Vesa Loitto ◽  
...  
Keyword(s):  
Diffusion Coefficient ◽  
Plasma Membrane ◽  
Membrane Proteins ◽  
Actin Polymerization ◽  
Correlation Spectroscopy ◽  
Image Correlation ◽  
Membrane Diffusion ◽  
Hek 293 ◽  
293 Cells ◽  
Aquaporin 9

The formation of nanodomains in the plasma membrane are thought to be part of membrane proteins regulation and signaling. Plasma membrane proteins are often investigated by analyzing the lateral mobility. k-space ICS (kICS) is a powerful image correlation spectroscopy (ICS) technique and a valuable supplement to fluorescence correlation spectroscopy (FCS). Here, we study the diffusion of aquaporin-9 (AQP9) in the plasma membrane, and the effect of different membrane and cytoskeleton affecting drugs, and therefore nanodomain perturbing, using kICS. We measured the diffusion coefficient of AQP9 after addition of these drugs using live cell Total Internal Reflection Fluorescence imaging on HEK-293 cells. The actin polymerization inhibitors Cytochalasin D and Latrunculin A do not affect the diffusion coefficient of AQP9. Methyl-β-Cyclodextrin decreases GFP-AQP9 diffusion coefficient in the plasma membrane. Human epidermal growth factor led to an increase in the diffusion coefficient of AQP9. These findings led to the conclusion that kICS can be used to measure diffusion AQP9, and suggests that the AQP9 is not part of nanodomains.

Effective Stiffness of a Debonded Particle in Particulate Composites

2007 ◽  
Vol 334-335 ◽  
pp. 33-36 ◽  
Author(s):  
Akihiro Wada ◽  
Yusuke Nagata ◽  
Shi Nya Motogi
Keyword(s):  
Three Dimensional ◽  
Particulate Composite ◽  
Spherical Particles ◽  
Particulate Composites ◽  
Particle Volume ◽  
Equivalent Inclusion Method ◽  
Equivalent Inclusion ◽  
Load Carrying ◽  
Dimensional Finite Element ◽  
Three Dimensional Finite Element

In this study, partially debonded spherical particles in a particulate composite are analyzed by three-dimensional finite element method to investigate their load carrying capacities, and the way to replace a debonded particle with an equivalent inclusion is examined. The variation in Young’s modulus and Poisson’s ratio of a composite with the debonded angle was evaluated for different particle arrangements and particle volume fractions, which in turn compared with the results derived from the equivalent inclusion method. Consequently, it was found that by replacing a debonded particle with an equivalent orthotropic one, the macroscopic behavior of the damaged composite could be reproduced so long as the interaction between neighboring particles is negligible.

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