Dataset Information

Simulation Study of Chain-like Body Translocation through Conical Pores in Thick Membranes.

ABSTRACT: Artificial membranes with conical pores and controllable thickness reveal ionic-transport capabilities that are superior compared with those offered by cylindrical pores. By simulating the translocation of an abstract chain-like body through a conical pore in a membrane with a variable thickness, we formulate a statistical model of the translocation time τ. Our rough model encodes the biochemical details of a given real chain-like molecule as evolving sequences of the allowed chain-like body's conformations. In our simulation experiments, we focus primarily on pore geometry and kinetic aspects of the translocation process. We study the impact of the membrane thickness L, and both conical-pore diameters ϕcis,ϕtrans on the probability distribution of τ. We have found that for all considered simulation setups, the randomness of τ is accurately described by the family of Moyal distributions while its expected value τ is proportional to Lξ, with ξ being dependent on ϕcis,ϕtrans.

SUBMITTER: Domanski Z

PROVIDER: S-EPMC8878698 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Simulation Study of Chain-like Body Translocation through Conical Pores in Thick Membranes.

Domański Zbigniew Z Grzybowski Andrzej Z AZ

Membranes 20220124 2

Artificial membranes with conical pores and controllable thickness reveal ionic-transport capabilities that are superior compared with those offered by cylindrical pores. By simulating the translocation of an abstract chain-like body through a conical pore in a membrane with a variable thickness, we formulate a statistical model of the translocation time τ. Our rough model encodes the biochemical details of a given real chain-like molecule as evolving sequences of the allowed chain-like body's c ...[more]

PMID: 35207060

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Project description:UnlabelledMembrane-active peptides, components of capsid structural proteins, assist viruses in overcoming the host membrane barrier in the initial stages of infection. Several such peptides have been identified, and their roles in membrane fusion or disruption have been characterized through biophysical studies. In several members of the Picornaviridae family, the role of the VP4 structural peptide in cellular-membrane penetration is well established. However, there is not much information on the membrane-penetrating capsid components of hepatitis A virus (HAV), an unusual member of this family. The VP4 peptide of HAV differs from its analogues in other picornaviruses in being significantly shorter in length and in lacking a signal for myristoylation, thought to be a critical requisite for VP4-mediated membrane penetration. Here we report, for the first time, that the atypical VP4 in HAV contains significant membrane-penetrating activity. Using a combination of biophysical assays and molecular dynamics simulation studies, we show that VP4 integrates into membrane vesicles through its N-terminal region to finally form discrete pores of 5- to 9-nm diameter, which induces leakage in the vesicles without altering their overall size or shape. We further demonstrate that the membrane activity of VP4 is specific toward vesicles mimicking the lipid content of late endosomes at acidic pH. Taken together, our data indicate that VP4 might be essential for the penetration of host endosomal membranes and release of the viral genome during HAV entry.ImportanceHepatitis A virus causes acute hepatitis in humans through the fecal-oral route and is particularly prevalent in underdeveloped regions with poor hygienic conditions. Although a vaccine for HAV exists, its high cost makes it unsuitable for universal application in developing countries. Studies on host-virus interaction for HAV have been hampered due to a lack of starting material, since the virus is extremely slow growing in culture. Among the unknown aspects of the HAV life cycle is its manner of host membrane penetration, which is one of the most important initial steps in viral infection. Here, we present data to suggest that a small peptide, VP4, a component of the HAV structural polyprotein, might be essential in helping the viral genome cross cell membranes during entry. It is hoped that this work might help in elucidating the manner of initial host cell interaction by HAV.

Dataset Information

Simulation Study of Chain-like Body Translocation through Conical Pores in Thick Membranes.

Publications

Simulation Study of Chain-like Body Translocation through Conical Pores in Thick Membranes.

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