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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 

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. 

Chromatin is an essential component of nuclear mechanical response and shape that maintains nuclear compartmentalization and function. However, major genomic functions, such as transcription activity, might also impact cell nuclear shape via blebbing and rupture through their effects on chromatin structure and dynamics. To test this idea, we inhibited transcription with several RNA polymerase II inhibitors in wild type cells and perturbed cells that present increased nuclear blebbing. Transcription inhibition suppresses nuclear blebbing for several cell types, nuclear perturbations, and transcription inhibitors. Furthermore, transcription inhibition suppresses nuclear bleb formation, bleb stabilization, and bleb-based nuclear ruptures. Interestingly, transcription inhibition does not alter either H3K9 histone modification state, nuclear rigidity, or actin compression and contraction, which typically control nuclear blebbing. Polymer simulations suggest that RNA pol II motor activity within chromatin could drive chromatin motions that deform the nuclear periphery. Our data provide evidence that transcription inhibition suppresses nuclear blebbing and rupture, separate and distinct from chromatin rigidity. 

ABSTRACT Rheology and the study of viscoelastic materials are an integral part of engineering and the study of biophysical systems. Tissue rheology is even used in the study of cancer and other diseases. However, the cost of a rheometer is feasible only for colleges, universities, and research laboratories. Even if a rheometer can be purchased, it is bulky and delicately calibrated, limiting its usefulness to the laboratory itself. The design presented here is less than a tenth of the cost of a professional rheometer. The design is also portable, making it the ideal solution to introduce viscoelasticity to high school students as well as for use in the field for obtaining rheological data.