scholarly journals Morphological control of receptor-mediated endocytosis

2021 ◽  
Author(s):  
Daniele Agostinelli ◽  
Gwynn J Elfring ◽  
Mattia Bacca

Receptor-mediated endocytosis is the primary process for nanoparticle uptake in cells and one of the main entry mechanisms for viral infection. The cell membrane adheres to the particle (nanoparticle or virus) and then wraps it to form a vesicle delivered to the cytosol. Previous findings identified a minimum radius for a spherical particle below which endocytosis cannot occur. This is due to the insufficient driving force, from receptor-ligand affinity, to overcome the energy barrier created by membrane bending. In this paper, we extend this result to the case of clathrin-mediated endocytosis, which is the most common pathway for virus entry. Moreover, we investigate the effect of ligand inhibitors on the particle surface, motivated by viral an- tibodies, peptides or phage capsids nanoparticles. We determine the necessary conditions for endocytosis by considering the additional energy barrier due to the membrane bending to wrap such inhibiting protrusions. We find that the density and size of inhibitors determine the size range of internalized particles, and endo- cytosis is completely blocked above critical thresholds. The assembly of a clathrin coat with a spontaneous curvature increases the energy barrier and sets a maximum particle size (in agreement with experimental observations on smooth particles). Our investigation suggests that morphological considerations can inform the optimal design of neutralizing viral antibodies and new strategies for targeted nanomedicine.

2014 ◽  
Vol 81 (8) ◽  
Author(s):  
Bin Chen

The cellular uptake of a particle through receptor-mediated endocytosis involves specific binding between ligands on the particle surface and diffusive receptors on the cell membrane. Since the rupture force of these specific bonds is generally random, the same can be the associated adhesion energy. To probe the effect of this randomness, we present a semistochastic model of receptor-mediated endocytosis, in which the adhesion energy between particle and membrane is regarded as a stochastic parameter obeying Boltzmann's distribution. It is shown that the so-called speed factor varies and that the rate of uptake is much lower than that from a previous deterministic model. It is also found that a spontaneous curvature can significantly increase the rate of uptake for particles of certain sizes. When constraining the random adhesion energy, we find that the rate of uptake can substantially increase. This work suggests that adhesion energy may be actively regulated during receptor-mediated endocytosis to improve the efficiency. By adopting random adhesion energy in the analysis, the physical picture of endocytosis implicated by the current work can be fundamentally different from that by a previous deterministic model.


Author(s):  
Eaton E. Lattman ◽  
Thomas D. Grant ◽  
Edward H. Snell

In this chapter we note that solution scattering data can be divided into four regions. At zero scattering angle, the scattering provides information on molecular weight of the particle in solution. Beyond that, the scattering is influenced by the radius of gyration. As the scattering angle increases, the scattering is influenced by the particle shape, and finally by the interface with the particle and the solution. There are a number of important invariants that can be calculated directly from the data including molecular mass, radius of gyration, Porod invariant, particle volume, maximum particle dimension, particle surface area, correlation length, and volume of correlation. The meaning of these is described in turn along with their mathematical derivations.


Soft Matter ◽  
2020 ◽  
Vol 16 (48) ◽  
pp. 10889-10899
Author(s):  
Rossana Rojas Molina ◽  
Susanne Liese ◽  
Haleh Alimohamadi ◽  
Padmini Rangamani ◽  
Andreas Carlson

A wide range of proteins create shape transformations of membranes. The remodeling is a coupling between the energetic cost of membrane bending, protein recruitment which induce local spontaneous curvature and protein diffusion on the membrane.


Author(s):  
Kem A. Sochacki ◽  
Bridgette L. Heine ◽  
Gideon J. Haber ◽  
John R. Jimah ◽  
Bijeta Prasai ◽  
...  

AbstractClathrin mediated endocytosis is the primary pathway for receptor and cargo internalization in eukaryotic cells. It is characterized by a polyhedral clathrin lattice that coats budding membranes. The mechanism and control of lattice assembly, curvature, and vesicle formation at the plasma membrane has been a matter of longstanding debate. Here, we use platinum replica and cryo electron microscopy and tomography to present a global structural framework of the pathway. We determine the shape and size parameters common to clathrin-mediated endocytosis. We show that clathrin sites maintain a constant surface area during curvature across multiple cell lines. Flat clathrin is present in all cells and spontaneously curves into coated pits without additional energy sources or recruited factors. Finally, we attribute curvature generation to loosely connected and pentagon-containing flat lattices that can rapidly curve when a flattening force is released. Together, these data present a new universal mechanistic model of clathrin-mediated endocytosis.


Membranes ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 516
Author(s):  
James M. Mangum ◽  
Ferdinand Harerimana ◽  
Millicent N. Gikunda ◽  
Paul M. Thibado

Electrically conductive, highly flexible graphene membranes hold great promise for harvesting energy from ambient vibrations. For this study, we built numerous three-dimensional graphene ripples, with each featuring a different amount of compression, and performed molecular dynamics simulations at elevated temperatures. These ripples have a convex cosine shape, then spontaneously invert their curvature to concave. The average time between inversion events increases with compression. We use this to determine how the energy barrier height depends on strain. A typical convex-to-concave curvature inversion process begins when the ripple’s maximum shifts sideways from the normal central position toward the fixed outer edge. The ripple’s maximum does not simply move downward toward its concave position. When the ripple’s maximum moves toward the outer edge, the opposite side of the ripple is pulled inward and downward, and it passes through the fixed outer edge first. The ripple’s maximum then quickly flips to the opposite side via snap-through buckling. This trajectory, along with local bond flexing, significantly lowers the energy barrier for inversion. The large-scale coherent movement of ripple atoms during curvature inversion is unique to two-dimensional materials. We demonstrate how this motion can induce an electrical current in a nearby circuit.


Author(s):  
Arijit Mahapatra ◽  
David Saintillan ◽  
Padmini Rangamani

AbstractCellular membranes are elastic lipid bilayers that contain a variety of proteins, including ion channels, receptors, and scaffolding proteins. These proteins are known to diffuse in the plane of the membrane and to influence the bending of the membrane. Experiments have shown that lipid flow in the plane of the membrane is closely coupled with the diffusion of proteins. Thus there is a need for a comprehensive framework that accounts for the interplay between these processes. Here, we present a theory for the coupled in-plane viscous flow of lipids, diffusion of transmembrane proteins, and curvature elastic deformation of lipid bilayers. The proteins in the membrane are modeled such that they influence membrane bending by inducing a spontaneous curvature. We formulate the free energy of the membrane with a Helfrich-like curvature elastic energy density function modified to account for the chemical potential energy of proteins. We derive the conservation laws and equations of motion for this system. Finally, we present results from dimensional analysis and numerical simulations and demonstrate the effect of coupled transport processes in governing the dynamics of membrane bending and protein diffusion.


Nanoscale ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 4545-4560 ◽  
Author(s):  
Zhiqiang Shen ◽  
Huilin Ye ◽  
Martin Kröger ◽  
Ying Li

The aggregation of PEG polymers during the membrane wrapping process of PEGylated liposomes can introduce a large free energy barrier, thereby limiting the cellular uptake of PEGylated liposomes.


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