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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 

Abstract Embedding a collective of tumor cells, i.e. a tumor spheroid, in a fibrous environment, such as a collagen network, provides an essentialin vitroplatform to investigate the biophysical mechanisms of tumor invasion. To predict new mechanisms, we develop a three-dimensional computational model of an embedded spheroid using a vertex model, with cells represented as deformable polyhedrons, mechanically coupled to a fiber network via active linker springs. As the linker springs actively contract, the fiber network remodels. As we tune the rheology of the spheroid and the fiber network stiffness, we find that both factors affect the remodeling of the fiber network with fluid-like spheroids densifying and radially realigning the fiber network more on average than solid-like spheroids but only for a range of intermediate fiber network stiffnesses. Our predictions are supported by experimental studies comparing non-tumorigenic MCF10A spheroids and malignant MDA-MB-231 spheroids embedded in collagen networks. The spheroid rheology-dependent effects are the result of cellular motility generating spheroid shape fluctuations. These shape fluctuations lead to emergent feedback between the spheroid and the fiber network to further remodel the fiber network. This emergent feedback occurs only at intermediate fiber network stiffness since at low fiber network stiffness, the mechanical response of the coupled system is dominated by the spheroid and for high fiber network stiffness, the mechanical response is dominated by the fiber network. We are therefore able to quantify the regime of optimal spheroid-fiber network mechanical reciprocity. Our results uncover intricate morphological-mechanical interplay between an embedded spheroid and its surrounding fiber network with both spheroid contractile strengthandspheroid shape fluctuations playing important roles in the pre-invasion stages of tumor invasion. 

The unique mechanical behaviors of actin–vimentin composites in both linear and nonlinear regimes are shaped by the complex interactions among actin entanglements, vimentin crosslinking, and poroelastic properties. 

The cytoskeleton is a complex network of interconnected biopolymers consisting of actin filaments, microtubules, and intermediate filaments. These biopolymers work in concert to transmit cell-generated forces to the extracellular matrix required for cell motility, wound healing, and tissue maintenance. While we know cell-generated forces are driven by actomyosin contractility and balanced by microtubule network resistance, the effect of intermediate filaments on cellular forces is unclear. Using a combination of theoretical modeling and experiments, we show that vimentin intermediate filaments tune cell stress by assisting in both actomyosin-based force transmission and reinforcement of microtubule networks under compression. We show that the competition between these two opposing effects of vimentin is regulated by the microenvironment stiffness. These results reconcile seemingly contradictory results in the literature and provide a unified description of vimentin’s effects on the transmission of cell contractile forces to the extracellular matrix. 

Vimentin, an intermediate filament protein typically located in the cytoplasm of mesenchymal cells, can also be secreted as an extracellular protein. The organization of extracellular vimentin strongly determines its functions in physiological and pathological conditions, making it a promising target for future therapeutic interventions. The extracellular form of vimentin has been found to play a role in the interaction between host cells and pathogens. In this review, we first discuss the molecular biophysics of extracellular vimentin, including its structure, secretion, and adhesion properties. We then provide a general overview of the role of extracellular vimentin in mediating pathogen-host interactions, with a focus on its interactions with viruses and bacteria. We also discuss the implications of these findings for the development of new therapeutic strategies for combating infectious diseases. 

The genotype-to-phenotype problem (G2P) for multicellular development asks how genetic inputs control collective phenotypic outputs. However, this is a challenging problem due to gene redundancy and stochasticity, causing mutations to have subtle phenotypic effects and replicates to display significant variation. We approach this problem using the model organism Myxococcus xanthus, a motile self-organizing bacterium that forms three-dimensional cell aggregates that mature into spore-filled fruiting bodies when under starvation stress. We develop a high-throughput imaging method using three-dimensional-printed microscopes to efficiently collect large phenotypic datasets. Our automated methods for analysis and visualization produce a map of phenotypic variation in M. xanthus development. We demonstrate that even subtle effects on developmental dynamics caused by mutation can be identified, discriminated, characterized, and given statistical significance, with implications for future gene annotation studies and the effect of environmental factors on G2P. 

Abstract The structure and dynamics of the cell nucleus regulate nearly every facet of the cell. Changes in nuclear shape limit cell motility and gene expression. Although the nucleus is generally seen as the stiffest organelle in the cell, cells can nevertheless deform the nucleus to large strains by small mechanical stresses. Here, we show that the mechanical response of the cell nucleus exhibits active fluidization that is driven by the BRG 1 motor of the SWI/SNF/BAF chromatin-remodeling complex. Atomic force microscopy measurements show that the nucleus alters stiffness in response to the cell substrate stiffness, which is retained after the nucleus is isolated and that the work of nuclear compression is mostly dissipated rather than elastically stored. Inhibiting BRG 1 stiffens the nucleus and eliminates dissipation and nuclear remodeling both in isolated nuclei and in intact cells. These findings demonstrate a novel link between nuclear motor activity and global nuclear mechanics. 

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.