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

2022 ◽  
Vol 137 (1) ◽  
Author(s):  
Raj Kumar Sadhu ◽  
Samo Penič ◽  
Aleš Iglič ◽  
Nir S. Gov
2018 ◽  
Vol 373 (1747) ◽  
pp. 20170115 ◽  
Author(s):  
N. S. Gov

Eukaryote cells have flexible membranes that allow them to have a variety of dynamical shapes. The shapes of the cells serve important biological functions, both for cells within an intact tissue, and during embryogenesis and cellular motility. How cells control their shapes and the structures that they form on their surface has been a subject of intensive biological research, exposing the building blocks that cells use to deform their membranes. These processes have also drawn the interest of theoretical physicists, aiming to develop models based on physics, chemistry and nonlinear dynamics. Such models explore quantitatively different possible mechanisms that the cells can employ to initiate the spontaneous formation of shapes and patterns on their membranes. We review here theoretical work where one such class of mechanisms was investigated: the coupling between curved membrane proteins, and the cytoskeletal forces that they recruit. Theory indicates that this coupling gives rise to a rich variety of membrane shapes and dynamics, while experiments indicate that this mechanism appears to drive many cellular shape changes. This article is part of the theme issue ‘Self-organization in cell biology’.


Soft Matter ◽  
2019 ◽  
Vol 15 (26) ◽  
pp. 5319-5330 ◽  
Author(s):  
Miha Fošnarič ◽  
Samo Penič ◽  
Aleš Iglič ◽  
Veronika Kralj-Iglič ◽  
Mitja Drab ◽  
...  

Simulations show that active protrusive forces induced by curved membrane proteins enhance their aggregation and drive a transition to flat pancake-shaped vesicles. This transition resembles the sheet-like protrusions (lamellipodia) of cells.


2022 ◽  
Author(s):  
Raj Kumar Sadhu ◽  
Sarah R. Barger ◽  
Samo Penic ◽  
Ales Iglic ◽  
Mira Krendel ◽  
...  

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.


2021 ◽  
Author(s):  
Raj Kumar Sadhu ◽  
Samo Penič ◽  
Aleš Iglič ◽  
Nir S. Gov

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.


Author(s):  
L. M. Marshall

A human erythroleukemic cell line, metabolically blocked in a late stage of erythropoiesis, becomes capable of differentiation along the normal pathway when grown in the presence of hemin. This process is characterized by hemoglobin synthesis followed by rearrangement of the plasma membrane proteins and culminates in asymmetrical cytokinesis in the absence of nuclear division. A reticulocyte-like cell buds from the nucleus-containing parent cell after erythrocyte specific membrane proteins have been sequestered into its membrane. In this process the parent cell faces two obstacles. First, to organize its erythrocyte specific proteins at one pole of the cell for inclusion in the reticulocyte; second, to reduce or abolish membrane protein turnover since hemoglobin is virtually the only protein being synthesized at this stage. A means of achieving redistribution and cessation of turnover could involve movement of membrane proteins by a directional lipid flow. Generation of a lipid flow towards one pole and accumulation of erythrocyte-specific membrane proteins could be achieved by clathrin coated pits which are implicated in membrane endocytosis, intracellular transport and turnover. In non-differentiating cells, membrane proteins are turned over and are random in surface distribution. If, however, the erythrocyte specific proteins in differentiating cells were excluded from endocytosing coated pits, not only would their turnover cease, but they would also tend to drift towards and collect at the site of endocytosis. This hypothesis requires that different protein species are endocytosed by the coated vesicles in non-differentiating than by differentiating cells.


Author(s):  
D.J. Benefiel ◽  
R.S. Weinstein

Intramembrane particles (IMP or MAP) are components of most biomembranes. They are visualized by freeze-fracture electron microscopy, and they probably represent replicas of integral membrane proteins. The presence of MAP in biomembranes has been extensively investigated but their detailed ultrastructure has been largely ignored. In this study, we have attempted to lay groundwork for a systematic evaluation of MAP ultrastructure. Using mathematical modeling methods, we have simulated the electron optical appearances of idealized globular proteins as they might be expected to appear in replicas under defined conditions. By comparing these images with the apearances of MAPs in replicas, we have attempted to evaluate dimensional and shape distortions that may be introduced by the freeze-fracture technique and further to deduce the actual shapes of integral membrane proteins from their freezefracture images.


Author(s):  
A. Engel ◽  
A. Holzenburg ◽  
K. Stauffer ◽  
J. Rosenbusch ◽  
U. Aebi

Reconstitution of solubilized and purified membrane proteins in the presence of phospholipids into vesicles allows their functions to be studied by simple bulk measurements (e.g. diffusion of differently sized solutes) or by conductance measurements after transformation into planar membranes. On the other hand, reconstitution into regular protein-lipid arrays, usually forming at a specific lipid-to-protein ratio, provides the basis for determining the 3-dimensional structure of membrane proteins employing the tools of electron crystallography.To refine reconstitution conditions for reproducibly inducing formation of large and highly ordered protein-lipid membranes that are suitable for both electron crystallography and patch clamping experiments aimed at their functional characterization, we built a flow-dialysis device that allows precise control of temperature and flow-rate (Fig. 1). The flow rate is generated by a peristaltic pump and can be adjusted from 1 to 500 ml/h. The dialysis buffer is brought to a preselected temperature during its travel through a meandering path before it enters the dialysis reservoir. A Z-80 based computer controls a Peltier element allowing the temperature profile to be programmed as function of time.


Author(s):  
Uwe Lücken ◽  
Joachim Jäger

TEM imaging of frozen-hydrated lipid vesicles has been done by several groups Thermotrophic and lyotrophic polymorphism has been reported. By using image processing, computer simulation and tilt experiments, we tried to learn about the influence of freezing-stress and defocus artifacts on the lipid polymorphism and fine structure of the bilayer profile. We show integrated membrane proteins do modulate the bilayer structure and the morphology of the vesicles.Phase transitions of DMPC vesicles were visualized after freezing under equilibrium conditions at different temperatures in a controlled-environment vitrification system. Below the main phase transition temperature of 24°C (Fig. 1), vesicles show a facetted appearance due to the quasicrystalline areas. A gradual increase in temperature leads to melting processes with different morphology in the bilayer profile. Far above the phase transition temperature the bilayer profile is still present. In the band-pass-filtered images (Fig. 2) no significant change in the width of the bilayer profile is visible.


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