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  1. 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. 
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    Free, publicly-accessible full text available December 1, 2025
  2. 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. 
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    Free, publicly-accessible full text available December 1, 2024
  3. 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. 
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    Free, publicly-accessible full text available December 1, 2024
  4. 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.

     
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  5. 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. However, as we learn more about the genetics and biochemistry of living systems, our understanding does not fully extend to the complex multiscale nature of how cells move, interact, and organize; this gap in understanding is referred to as the genotype-to-phenotype problem. The physics of soft matter sets the background on which living organisms evolved, and the cell environment is a strong determinant of cell phenotype. This inevitably leads to challenges as the full function of many genes, and the diversity of cellular behaviors cannot be assessed without wide screens of environmental conditions. Cellular mechanobiology is an emerging field that provides methodologies to understand how cells integrate chemical and physical environmental stress and signals, and how they are transduced to control cell function. Biofilm forming bacteria represent an attractive model because they are fast growing, genetically malleable and can display sophisticated self-organizing developmental behaviors similar to those found in higher organisms. Here, we propose mechanobiology as a new area of study in prokaryotic systems and describe its potential for unveiling new links between an organism's genome and phenome. 
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  6. 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). It was demonstrated that the incorporation of unnatural AzAla tryptophan analog residue improves the antimicrobial properties of the hydrogel. The material developed can have a practical application and be a paradigm shift in the approach to wound treatment, and it will improve healing outcomes for millions of patients each year.

     
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  7. null (Ed.)