Metabolically intact nuclei are fluidized by the activity of the chromatin remodeling motor BRG1.

The structure and dynamics of the nucleus regulate cellular functions, with shape changes impacting cell motility. 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 BRG1 motor of the SWI/SNF/BAF chromatin remodeling complex.

Reorganizing chromatin by cellular deformation.

Biologists have the capability to edit a genome at the nanometer scale and then observe whether or not the edit affects the structure of a developing organ or organism at the centimeter scale. Our understanding of the underlying mechanisms driving this emergent phenomenon from a multiscale perspective remains incomplete. This review focuses predominantly on recent experimental developments in uncovering the mechanical interplay between the chromatin and cell scale since mechanics plays a major role in determining nuclear, cellular, and tissue structure.

Vimentin promotes collective cell migration through collagen networks via increased matrix remodeling and spheroid fluidity.

The intermediate filament (IF) protein vimentin is associated with many diseases with phenotypes of enhanced cellular migration and aggressive invasion through the extracellular matrix (ECM) of tissues, but vimentin's role in in-vivo cell migration is still largely unclear. Vimentin is important for proper cellular adhesion and force generation, which are critical to cell migration; yet the vimentin cytoskeleton also hinders the ability of cells to squeeze through small pores in ECM, resisting migration. To identify the role of vimentin in collective cell migration, we generate spheroids of wide-type and vimentin-null mouse embryonic fibroblasts (mEFs) and embed them in a 3D collagen matrix.

Switchable microscale stress response of actin-vimentin composites emerges from scale-dependent interactions.

The mechanical properties of the mammalian cell regulate many cellular functions and are largely dictated by the cytoskeleton, a composite network of protein filaments, including actin, microtubules, and intermediate filaments. Interactions between these distinct filaments give rise to emergent mechanical properties that are difficult to generate synthetically, and recent studies have made great strides in advancing our understanding of the mechanical interplay between actin and microtubule filaments. While intermediate filaments play critical roles in the stress response of cells, their effect on the rheological properties of the composite cytoskeleton remains poorly understood.

Vimentin supports cell polarization by enhancing centrosome function and microtubule acetylation.

Cell polarity is important for controlling cell shape, motility and cell division processes. Vimentin intermediate filaments are important for cell migration and cell polarization in mesenchymal cells and assembly of vimentin and microtubule networks is dynamically coordinated, but the precise details of how vimentin mediates cell polarity remain unclear. Here, we characterize the effects of vimentin on the structure and function of the centrosome and the stability of microtubule filaments in wild-type and vimentin-null mouse embryonic fibroblasts.

Vimentin is a key regulator of cell mechanosensing through opposite actions on actomyosin and microtubule networks.

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.

Metabolically intact nuclei are fluidized by the activity of the chromatin remodeling motor BRG1.

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.

Enhanced extracellular matrix remodeling due to embedded spheroid fluidization.

Tumor spheroids are in vitro three-dimensional, cellular collectives consisting of cancerous cells. Embedding these spheroids in an in vitro fibrous environment, such as a collagen network, to mimic the extracellular matrix (ECM) provides an essential platform to quantitatively investigate the biophysical mechanisms leading to tumor invasion of the ECM. To understand the mechanical interplay between tumor spheroids and the ECM, we computationally construct and study a three-dimensional vertex model for a tumor spheroid that is mechanically coupled to a cross-linked network of fibers.

Mechanobiology as a tool for addressing the genotype-to-phenotype problem in microbiology.

The central hypothesis of the genotype-phenotype relationship is that the phenotype of a developing organism (i.e., its set of observable attributes) depends on its genome and the environment.

Bacteria Colonies Modify Their Shear and Compressive Mechanical Properties in Response to Different Growth Substrates.

Bacteria build multicellular communities termed biofilms, which are often encased in a self-secreted extracellular matrix that gives the community mechanical strength and protection against harsh chemicals. How bacteria assemble distinct multicellular structures in response to different environmental conditions remains incompletely understood. Here, we investigated the connection between bacteria colony mechanics and the colony growth substrate by measuring the oscillatory shear and compressive rheology of bacteria colonies grown on agar substrates.

A Torsion-Based Rheometer for Measuring Viscoelastic Material Properties.

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.

Vimentin takes a hike - Emerging roles of extracellular vimentin in cancer and wound healing.

Vimentin is a cytoskeletal protein important for many cellular processes, including proliferation, migration, invasion, stress resistance, signaling, and many more. The vimentin-deficient mouse has revealed many of these functions as it has numerous severe phenotypes, many of which are found only following a suitable challenge or stress. While these functions are usually related to vimentin as a major intracellular protein, vimentin is also emerging as an extracellular protein, exposed at the cell surface in an oligomeric form or secreted to the extracellular environment in soluble and vesicle-bound forms.

Transcription inhibition suppresses nuclear blebbing and rupture independently of nuclear rigidity.

Chromatin plays an essential role in the nuclear mechanical response and determining nuclear shape, which maintain 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 presented increased nuclear blebbing.

The molecular biophysics of extracellular vimentin and its role in pathogen-host interactions.

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.

Antibacterial and Cytocompatible pH-Responsive Peptide Hydrogel.

A short peptide, FHHF-11, was designed to change stiffness as a function of pH due to changing degree of protonation of histidines. As pH changes in the physiologically relevant range, G' was measured at 0 Pa (pH 6) and 50,000 Pa (pH 8). This peptide-based hydrogel is antimicrobial and cytocompatible with skin cells (fibroblasts).

Vimentin supports cell polarization by enhancing centrosome function and microtubule acetylation.

Cell polarity is important for controlling cell shape, motility, and cell division processes. Vimentin intermediate filaments are necessary for proper polarization of migrating fibroblasts and assembly of vimentin and microtubule networks is dynamically coordinated, but the precise details of how vimentin mediates cell polarity remain unclear. Here, we characterize the effects of vimentin on the structure and function of the centrosome and the stability of microtubule filaments in wild-type and vimentin-null mouse embryonic fibroblasts (mEFs).

How cells wrap around virus-like particles using extracellular filamentous protein structures.

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.

How cells wrap around virus-like particles using extracellular filamentous protein structures.

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.

Spreading rates of bacterial colonies depend on substrate stiffness and permeability.

The ability of bacteria to colonize and grow on different surfaces is an essential process for biofilm development. Here, we report the use of synthetic hydrogels with tunable stiffness and porosity to assess physical effects of the substrate on biofilm development. Using time-lapse microscopy to track the growth of expanding colonies, we find that biofilm colony growth can increase with increasing substrate stiffness, unlike what is found on traditional agar substrates.

Dynamic remodeling of fiber networks with stiff inclusions under compressive loading.

The ability of tissues to sustain and withstand mechanical stress is critical to tissue development and healthy tissue maintenance. The mechanical properties of tissues are typically considered to be dominated by the fibrous extracellular matrix (ECM) component of tissues. Fiber network mechanics can capture certain mechanical features of tissues, such as shear strain stiffening, but is insufficient in describing the compressive response of certain tissues and blood clots that are rich in extracellular matrix.

Unique Role of Vimentin Networks in Compression Stiffening of Cells and Protection of Nuclei from Compressive Stress.

In this work, we investigate whether stiffening in compression is a feature of single cells and whether the intracellular polymer networks that comprise the cytoskeleton (all of which stiffen with increasing shear strain) stiffen or soften when subjected to compressive strains. We find that individual cells, such as fibroblasts, stiffen at physiologically relevant compressive strains, but genetic ablation of vimentin diminishes this effect. Further, we show that unlike networks of purified F-actin or microtubules, which soften in compression, vimentin intermediate filament networks stiffen in both compression and extension, and we present a theoretical model to explain this response based on the flexibility of vimentin filaments and their surface charge, which resists volume changes of the network under compression.

The role of vimentin-nuclear interactions in persistent cell motility through confined spaces.

The ability of cells to move through small spaces depends on the mechanical properties of the cellular cytoskeleton and on nuclear deformability. In mammalian cells, the cytoskeleton is composed of three interacting, semi-flexible polymer networks: actin, microtubules, and intermediate filaments (IF). Recent experiments of mouse embryonic fibroblasts with and without vimentin have shown that the IF vimentin plays a role in confined cell motility.