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Nanoparticles, such as viruses, can enter cells via endocytosis, a process by which the cell membrane wraps around them. The role of nanoparticle size and shape on endocytosis has been well studied, but the biophysical details of how extracellular proteins on the cell membrane surface mediate uptake are less clear. Motivated by recent discoveries regarding extracellular vimentin in viral and bacterial uptake and the structure of coronaviruses, we construct a computational model with a cell-like and virus-like construct containing filamentous protein structures protruding from their surfaces. We study the impact of these additional degrees of freedom on viral wrapping. The cell surface is modeled as a deformable sheet with bending rigidity, and extracellular vimentin as semiflexible polymers, or extracellular components (ECC), placed randomly on the sheet. The virus is modeled as a deformable shell that also has explicit, freely rotating spike filaments on its surface. Our results indicate that cells with optimally populated filaments are more susceptible to infection as they take up the virus more quickly and utilize a relatively smaller area of the cell surface. At optimal ECC density, the cell surface forms a fold around the virus, which is faster and more efficient at wrapping than localized crumples. Additionally, cell surface bending rigidity aids in the generation of folds by increasing force transmission across the surface. Changing other mechanical parameters, such as the stretching stiffness of filamentous ECC or virus spikes, can result in localized crumple formation on the cell surface. We conclude with the implications of our study on the evolutionary pressures of virus-like particles, with a particular focus on the cellular microenvironment. Published by the American Physical Society2025
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Penetration of Cell Surface Glycocalyx by Enveloped Viruses Is Aided by Weak Multivalent Adhesive Interaction
Viral infection usually begins with adhesion between the viral particle and viral receptors displayed on the cell membrane. The exterior surface of the cell membrane is typically coated with a brush-like layer of molecules, the glycocalyx, that the viruses need to penetrate. Although there is extensive literature on the biomechanics of virus−cell adhesion, much of it is based on continuum-level models that do not address the question of how virus/cell-membrane adhesion occurs through the glycocalyx. In this work, we present a simulation study of the penetration mechanism. Using a coarse-grained molecular model, we study the force-driven and di"usive penetration of a brush-like glycocalyx by viral particles. For force-driven penetration, we find that viral particles smaller than the spacing of molecules in the brush reach the membrane surface readily. For a given maximum force, viral particles larger than the minimum spacing of brush molecules arrest at some distance from the membrane, governed by the balance of elastic and applied forces. For the di"usive case, we find that weak but multivalent attraction between the glycocalyx molecules and the virus e"ectively leads to its engulfment by the glycocalyx. Our finding provides potential guidance for developing glycocalyx-targeting drugs and therapies by understanding how virus−cell adhesion works.
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- Award ID(s):
- 2200066
- PAR ID:
- 10621447
- Publisher / Repository:
- ACS
- Date Published:
- Journal Name:
- The Journal of Physical Chemistry B
- Volume:
- 127
- Issue:
- 2
- ISSN:
- 1520-6106
- Page Range / eLocation ID:
- 486 to 494
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Nanoparticles, such as viruses, can enter cells via endocytosis. During endocytosis, the cell surface wraps around the nanoparticle to effectively eat it. Prior focus has been on how nanoparticle size and shape impacts endocytosis. However, inspired by the noted presence of extracellular vimentin affecting viral and bacteria uptake, as well as the structure of coronaviruses, we construct a computational model in whichboththe cell-like construct and the virus-like construct contain filamentous protein structures protruding from their surfaces. We then study the impact of these additional degrees of freedom on viral wrapping. We find that cells with an optimal density of filamentous extracellular components (ECCs) are more likely to be infected as they uptake the virus faster and use relatively less cell surface area per individual virus. At the optimal density, the cell surface folds around the virus, and folds are faster and more efficient at wrapping the virus than crumple-like wrapping. We also find that cell surface bending rigidity helps generate folds, as bending rigidity enhances force transmission across the surface. However, changing other mechanical parameters, such as the stretching stiffness of filamentous ECCs or virus spikes, can drive crumple-like formation of the cell surface. We conclude with the implications of our study on the evolutionary pressures of virus-like particles, with a particular focus on the cellular microenvironment that may include filamentous ECCs.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acs.jpcb.2c06662
