Biology subjects

Schneider, S. E.

Publications and source records attributed to Schneider, S. E..

15 recordsLinked to original sources

bioRxiv2026

Particle-Only gECM Wafers Enable Cohesive, ECM-Rich Scaffolds Without Secondary Polymers

Granular extracellular matrix (gECM)-based biomaterials commonly contain polymer components to improve scaffold cohesion and handling during fabrication and use. However, these polymer hydrogel components may dilute ECM content and increase fabrication and regulatory complexity. This study evaluated whether particle-only gECM wafers could serve as a simplified alternative to hydrogel-based gECM scaffolds while maintaining structural, mechanical, and biological performance. Decellularized human cartilage and skin tissues were processed and fabricated into three scaffold formats: gECM hydrogels, freeze-dried gECM hydrogel wafers, and freeze-dried particle-only gECM wafers. Across fabrication methods, scaffold swelling, volume fraction, and stiffness were strongly influenced by both tissue type and fabrication approach. gECM hydrogels exhibited the greatest swelling and lowest stiffness, while gECM wafers displayed higher volume fractions and greater mechanical stiffness. Notably, gECM particle-only wafers achieved performance comparable to gECM hydrogel wafers despite the absence of a secondary polymer network. Particle-only wafers also maintained swelling behavior and structural properties over 3 months of dry storage at room temperature, with only modest decreases in stiffness. In vitro studies showed sustained cell viability over 14 days on particle-only wafers, with chondrocytes infiltrating cartilage wafers and fibroblasts remaining primarily surface-localized on skin wafers. In addition, particle-only wafers remained cohesive during implantation into a bovine cartilage defect model. These findings demonstrate that particle-only gECM wafers can achieve structural integrity, mechanical performance, and cytocompatibility without the need for an additional polymer network, highlighting a simplified and ECM-rich biomaterial platform. By eliminating polymer carriers and enabling dry storage with preserved function, this approach supports the development of off-the-shelf, translationally accessible gECM particle-only wafers for tissue engineering applications.

bioengineering↗

bioRxiv2026

Human Osteochondral Granular Extracellular Matrix (gECM) Hydrogels Drive Tissue-Specific Composition and Mechanics

Osteochondral defects remain a major clinical challenge due to the limited regenerative capacity of cartilage and the complexity of the osteochondral interface. Here, we present a human-derived granular extracellular matrix (gECM) hydrogel platform designed for translational osteochondral repair. Using otherwise discarded human donor tissues, we developed cartilage and bone gECM hydrogels under current good manufacturing practice workflows. These materials are shear-thinning, immediately hold their form, and crosslink under physiological conditions to form stable constructs. Proteomic analysis confirmed that cartilage and bone gECM retain distinct tissue-specific biochemical signatures, while mechanical characterization demonstrated tissue-relevant stiffness, with bone gECM hydrogels exhibiting greater stiffness than cartilage gECM hydrogel. Particle packing density primarily governed viscosity, whereas tissue type contributed strongly to bulk stiffness. Together, these findings establish a scalable, human-derived gECM platform that integrates tissue-specific structural and mechanical cues, and advances a clinically translatable strategy for osteochondral repair.

bioengineering↗

bioRxiv2026

Lamin A/C coordinates nuclear mechanics, chromatin architecture, and transcriptional homeostasis in skeletal muscle in vivo

The nuclear lamina provides mechanical integrity to the eukaryotic nucleus and organizes lamina-associated chromatin domains that are important for chromatin architecture and gene-expression regulation. Lamin A/C, a major component of the nuclear lamina, is disrupted in hereditary laminopathies and has also been implicated in aging-associated nuclear dysfunction. Although the mechanical role of Lamin A/C has been extensively studied in vitro, particularly in monolayer cell culture and isolated nuclei, its role in maintaining nuclear mechanics and chromatin organization in intact tissues remains incompletely understood. Here, we investigated how partial and complete Lamin A/C disruption affects nuclear shape, chromatin architecture, intranuclear mechanics, and gene expression in vivo. Across multiple murine tissues, Lamin A/C deficiency did not cause a generalized collapse of nuclear shape or gross tissue architecture. Instead, Lamin A/C disruption preferentially altered chromatin architecture in mechanically stiff tissues, including skeletal muscle and heart. Using live in vivo deformation microscopy during controlled hindlimb muscle stimulation, we quantified real-time multiscale deformation of skeletal muscle tissue and nuclei. These measurements revealed reduced effective nuclear stiffness and altered load sharing between euchromatin-rich and heterochromatin-rich domains after Lamin A/C loss. Super-resolution imaging further showed that partial and complete Lamin A/C disruption uncoupled H3K9me3 from DAPI-dense heterochromatin, indicating a spatial disruption of repressive chromatin organization. Exploratory ATAC-seq suggested increased chromatin accessibility in heterozygous muscle, whereas RNA-seq showed that complete Lamin A/C loss caused broad myopathic transcriptional dysregulation while partial loss preserved a near-wild-type transcriptomic state. Integrated analysis identified HDAC2 as a candidate mechanosensitive compensatory node that may help buffer gene expression after partial Lamin A/C disruption. Together, these results establish Lamin A/C as an in vivo coordinator of nuclear mechanics, heterochromatin organization, and transcriptional homeostasis in skeletal muscle.

cell biology↗

bioRxiv2026

Granular Extracellular Matrix (gECM) Hydrogel Wafers as Shelf-Stable 2.5D Substrates for Microphysiological Modeling

Understanding disease pathology and evaluating emerging therapeutics require in vitro models that accurately recapitulate human tissue environments. However, existing microphysiological systems often compromise either biomimicry or ease-of-use, limiting widespread adoption and scalability. Here, we present lyophilized granular extracellular matrix (gECM) hydrogel wafers as shelf-stable, humanized 2.5D substrates that enable physiologically relevant modeling while simplifying integration into experimental workflows. Derived from decellularized human cartilage and bone, gECM hydrogel wafers retain tissue-specific architecture while introducing microporosity and surface topography through lyophilization. These wafers maintain swelling behavior, structural integrity, and mechanical properties over three months of room-temperature storage, allowing pre-fabrication and on-demand use without loss of function. gECM hydrogel wafers support direct cell seeding without encapsulation and sustain viability and proliferation of human adipose-derived mesenchymal stromal cells over 21 days, with gene expression trends comparable to 3D gECM hydrogels. Furthermore, wafers can be readily integrated into microfluidic systems with in situ hydration and transport of large biomolecules. Together, this platform bridges the gap between conventional 2D culture ease-of-use and 3D biomaterial biomimicry, providing a scalable and physiologically relevant in vitro model approach for high-throughput disease studies and therapeutic screening.

bioengineering↗

bioRxiv2026

Multi-step femtosecond laser-fabricated membranes for regulated migration of biomolecules and cells

Organ-on-chip (OoC) systems enable the recapitulation of key structural and functional characteristics of human tissues within controlled micro-engineered environments. In mechanically active tissues such as musculoskeletal, cardiac, and vascular systems, the incorporation of dynamic physical forces is essential for replicating the biomechanical cues governing cellular morphology and functional responses in-vivo. Without such stimuli, OoC models may fail to capture physiologically relevant tissue behaviors. Porous and semi-permeable membranes are critical components of OoCs, facilitating selective transport of nutrients, gases, and signaling molecules between cellular compartments to support biologically accurate barrier replication. Hence, fabrication strategies that permit precise modulation of membrane permeability are desirable to accommodate for the varying needs in pore size and porosity across organ systems. This study presents a two-stage fabrication process for stretchable, microporous polydimethylsiloxane (PDMS) membranes using femtosecond (fs-) pulse laser drilling. The laser-ablated pores exhibit a characteristic conical morphology, with diameters tapering from the laser entry to exit point. By modulating laser power and number of pulses, 6-15 m exit-end pore diameters were achieved in 50 m thick PDMS films. The membranes demonstrated strong mechanical resilience, with a 5-12% reduction in Youngs modulus after 500 cycles of strain loading. Furthermore, membranes fabricated at lower laser powers exhibited superior retention of elasticity, highlighting the influence of processing parameters on mechanical behavior. Cytocompatibility and permeability assessments confirmed that the membranes supported sustained cell viability and proliferation over at least three days. In size-restricted membrane pore geometries, cellular migration was constrained without any inhibition of biomolecular transport. This selective permeability is critical in multilayer OoC architectures, where a balance between biomolecular diffusion and cellular compartmentalization is necessary to preserve distinct tissue interfaces and functional organization. This work presents fs-laser micro-drilling as a robust and tunable fabrication strategy for producing mechanically resilient, selectively permeable PDMS membranes for physiologically relevant OoC applications.

bioengineering↗

bioRxiv2026

Granular Extracellular Matrix (gECM) Hydrogels Enable Distinct Composition and Mechanics Across Tissue Types for Translation

Biomaterials-based tissue engineering aims to recapitulate native tissue architecture and function for both clinical repair and advanced in vitro models. While improvements in biomaterials have been made, including granular hydrogels and ECM-derived scaffolds, current biomaterials lack intentional design choices for effective translation, including regulatory considerations, practical extrusion delivery, and biomimetic characteristics. Here, we develop and characterize a library of granular ECM (gECM) biomaterials for five key tissues (cartilage, bone, skin, liver, and kidney), in which ECM particles are densely packed within a hyaluronic acid hydrogel. We optimize tissue processing methods that preserve proteomic content and structure while also aligning with scale-up manufacturing and regulatory guidelines. We show that gECM hydrogels can be molded, extruded, and 3D-printed while retaining their shape, and they stabilize at physiological temperature and pH. Lastly, we demonstrate that bulk gECM mechanics are driven by tissue type, and gECM hydrogels support viability, proliferation, and tissue-specific cellular activity. Together, these findings establish gECM hydrogels as a translational and biomimetic platform for clinical tissue repair and complex in vitro models.

bioengineering↗

bioRxiv2026

Flowable Grafts Made from Granular Extracellular Matrix (gECM) Hydrogels Promote Integrative Repair of Articular Cartilage in a Large-Animal Model

Focal injuries to articular cartilage in load-bearing joints fail to heal and often progress to degeneration, underscoring the need for repair strategies that result in restored cartilage structure and function rather than fibrocartilage formation. Granular extracellular matrix (gECM) hydrogels, flowable grafts composed of densely-packed matrix particles, offer a promising approach but lack long-term functional validation in large-animal models. Here, we developed a flowable gECM hydrogel composed of decellularized cartilage microparticles incorporated within a thiol-functionalized hyaluronan matrix. Proteomic analysis confirmed enrichment of cartilage-specific gECM matrisome components. When implanted into critical-sized femoral condyle defects in a goat model and evaluated 12 months post-implantation, both gECM hydrogel and microdrilling (surgical controls) achieved >80% defect filling. However, in contrast to microdrilling, gECM repair tissue exhibited surface tribological (friction, adhesion) and compressive mechanical properties comparable to native cartilage, with a similar proteoglycan-to-collagen ratio, enrichment of type II collagen, minimal type I collagen (typical of a fibrous scar), improved quantitative MRI metrics, and evidence of lateral cartilage integration and subchondral bone remodeling. Together, these findings demonstrate that a flowable gECM hydrogel supports integrative, cartilage-like repair in a load-bearing joint, supporting advancement of this approach toward clinical translation. One Sentence SummaryA granular ECM hydrogel implanted in a goat condyle provided a robust repair, filling the defect tissue with integrated, hyaline-like cartilage at 12 months.

bioengineering↗

bioRxiv2023

Multi-frame biomechanical and relaxometry analysis during in vivo loading of the human knee by spiral dualMRI and compressed sensing

PurposeKnee cartilage experiences repetitive loading during physical activities, which is altered during the pathogenesis of diseases like osteoarthritis. Analyzing the biomechanics during motion provides a clear understanding of the dynamics of cartilage deformation, and may establish essential imaging biomarkers of early-stage disease. However, in vivo biomechanical analysis of cartilage during rapid motion is not well established. MethodsWe used spiral DENSE MRI on in vivo human tibiofemoral cartilage during cyclic varus loading (0.5 Hz) and employed compressed sensing on the k-space data. The applied compressive load was set for each participant at 0.5x body weight on the medial condyle. Relaxometry methods were measured on the cartilage before (T1{rho}, T2) and after (T1{rho}) varus load. ResultsDisplacement and strain maps showed a gradual shift of displacement and strain in time. Compressive strain was observed in the medial condyle cartilage and shear strain was roughly half of the compressive strain. Male participants had more displacement in the loading direction compared to females, and T1{rho} values did not change after cyclic varus load. Compressed sensing reduced the scanning time up to 25-40% when comparing the displacement maps and substantially lowered the noise levels. ConclusionThese results demonstrated the ease of which spiral DENSE MRI could be applied to clinical studies due to the shortened imaging time, while quantifying realistic cartilage deformations that occur through daily activities, and that could serve as biomarkers of early osteoarthritis.

bioengineering↗

bioRxiv2022

Epigenetic Priming Enhances Chondrogenic Potential of Expanded Chondrocytes for Cartilage Repair

Expansion of chondrocytes presents a major obstacle in the cartilage regeneration procedure matrix-induced autologous chondrocyte implantation (MACI). Dedifferentiation of chondrocytes during the expansion process leads to the emergence of a fibrotic (chondrofibrotic) phenotype that decreases the chondrogenic potential of the implanted cells. We aim to 1) determine the extent that chromatin architecture of H3K27me3 and H3K9me3 remodels during dedifferentiation and persists when expanded chondrocytes are transferred to a 3D culture; and 2) to prevent this persistent remodeling to enhance the chondrogenic potential of expanded chondrocytes. Chromatin architecture remodeling of H3K27me3 and H3K9me3 was observed at 0, 8 and 16 population doublings in a two-dimensional (2D) culture and after encapsulation of the expanded chondrocytes in a three-dimensional (3D) hydrogel culture. Chondrocytes were treated with inhibitors of epigenetic modifiers (epigenetic priming) for 16 population doublings and then encapsulated in 3D hydrogels. Chromatin architecture of chondrocytes and gene expression were evaluated before and after encapsulation. We observed a change in chromatin architecture of epigenetic modifications H3K27me3 and H3K9me3 during chondrocyte dedifferentiation. Although inhibiting enzymes that modify H3K27me3 and H3K9me3 did not alter the dedifferentiation process in 2D culture, applying these treatments during the 2D expansion did increase the expression of select chondrogenic genes and protein deposition of type II collagen when transferred to a 3D environment. Overall, we found that epigenetic priming of expanded chondrocytes alters the cell fate when chondrocytes are later encapsulated into a 3D environment, providing a potential method to enhance the success of cartilage regeneration procedures.

bioengineering↗

bioRxiv2022

High-frame-rate analysis of knee cartilage deformation by spiral dualMRI and relaxation mapping

PurposeDaily activities including walking impose high frequency cyclic forces on cartilage and repetitive compressive deformation. Analyzing cartilage deformation during walking would provide spatial maps of displacement, strain, and enable viscoelastic characterization, which may serve as imaging biomarkers for early cartilage degeneration when the damage is still reversible. However, the time-dependent biomechanics of cartilage is not well described, and how defects in the joint impact the viscoelastic response is unclear. MethodsWe used spiral acquisition with displacement encoding MRI to quantify displacement and strain maps at a high frame rate (40 ms; 25 frames/sec) in tibiofemoral joints. We also employed relaxometry methods (T1, T1{rho}, T2, T2*) on the cartilage. ResultsNormal and shear strains were concentrated on the tibiofemoral contact area during loading, and the defected joint exhibited larger compressive strains. We also determined a positive correlation between the change of T1{rho} in cartilage after cyclic loading and increased compressive strain on the defected joint. Viscoelastic behavior was quantified by the time-dependent displacement, where the damaged joint showed increased creep behavior compared to the intact. ConclusionsOur results indicate that spiral scanning with displacement encoding can quantitatively differentiate the damaged from intact joint using the strain and creep response. The viscoelastic response identified with this methodology could serve as biomarkers to detect defects in joints in vivo and facilitate the early diagnosis of joint diseases such as osteoarthritis.

bioengineering↗

bioRxiv2021

Epigenetic remodeling during monolayer cell expansion reduces therapeutic potential

Understanding how cells remember previous mechanical environments to influence their fate, or mechanical memory, informs the design of biomaterials and therapies in medicine. Current regeneration therapies require two-dimensional (2D) cell expansion processes to achieve large cell populations critical for the repair of damaged (e.g. connective and musculoskeletal) tissues. However, the influence of mechanical memory on cell fate following expansion is unknown, and mechanisms defining how physical environments influence the therapeutic potential of cells remain poorly understood. Here, we show that the organization of histone H3 trimethylated at lysine 9 (H3K9me3) and expression of tissue-identifying genes in primary cartilage cells (chondrocytes) transferred to three-dimensional (3D) hydrogels depends on the number of previous population doublings on tissue culture plastic during 2D cell expansion. Decreased levels of H3K9me3 occupying promoters of dedifferentiation genes after the 2D culture were also retained in 3D culture. Suppression of H3K9me3 during expansion of cells isolated from a murine model similarly resulted in the loss of the chondrocyte phenotype and global remodeling of nuclear architecture. In contrast, increasing levels of H3K9me3 through inhibiting H3K9 demethylases partially rescued the chondrogenic nuclear architecture and gene expression, which has important implications for tissue repair therapies, where expansion of large numbers of phenotypically-suitable cells is required. Overall, our findings indicate mechanical memory in primary cells is encoded in the chromatin architecture, which impacts cell fate and the phenotype of expanded cells. SIGNIFICANCE STATEMENTTissue regeneration procedures, such as cartilage defect repair (e.g. Matrix-induced Autologous Chondrocyte Implantation) often require cell expansion processes to achieve sufficient cells to transplant into an in vivo environment. However, the chondrocyte cell expansion on 2D stiff substrates induces epigenetic changes that persist even when the chondrocytes are transferred to a different (e.g. 3D) or in vivo environment. Treatments to alter epigenetic gene regulation may be a viable strategy to improve existing cartilage defect repair procedures and other tissue engineering procedures that involve cell expansion.

bioengineering↗

bioRxiv2021

Dedifferentiation alters chondrocyte nuclear mechanics during in vitro culture and expansion

Dedifferentiation of chondrocytes during in vitro passaging before implantation, and post implantation in vivo, is a critical limitation in cartilage tissue engineering. Several biophysical features define the dedifferentiated state including a flattened cell morphology and increased stress fiber formation. However, how dedifferentiation influences nuclear mechanics, and the possible long-term implications of this state, are unknown. In this study, we investigated how chondrocyte dedifferentiation affects the mechanics of the chromatin architecture inside the cell nucleus and the gene expression of the structural proteins located at the nuclear envelope. Through an experimental model of cell stretching and a detailed spatial intranuclear strain quantification, we identified that strain is amplified and distribution of strain within the chromatin is altered under tensile loading in the dedifferentiated state. Further, using a confocal microscopy image-based finite element model and simulation of cell stretching, we found that the cell shape is the primary determinant of the strain amplification inside the chondrocyte nucleus in the dedifferentiated state. Additionally, we found that nuclear envelope proteins have lower gene expression in the dedifferentiated state suggesting a weaker nuclear envelope which can further intensify the intranuclear strain amplification. Our results indicate that dedifferentiation and altered nuclear strain could promote gene expression changes at the nuclear envelope, thus promoting further deviation from chondrocyte phenotype. This study highlights the role of cell shape on nuclear mechanics and lays the groundwork to design biophysical strategies for the maintenance and enhancement of the chondrocyte phenotype during expansion with a goal of successful cartilage tissue engineering. SIGNIFICANCEChondrocytes dedifferentiate into a fibroblast-like phenotype in a non-native biophysical environment. Using high resolution microscopy, intranuclear strain analysis, finite element method based computational modeling, and molecular biology techniques, we investigated how mechanical force causes abnormal intranuclear strain distribution in chondrocytes during the dedifferentiation process. Overall, our results suggest that the altered cell geometry aided by an altered or weakened nuclear envelope structure are responsible for abnormal intranuclear strain during chondrocyte dedifferentiation that can further deviate chondrocytes to a more dedifferentiated state.

biophysics↗

bioRxiv2020

Helicobacter pylori diversification during chronic infection within a single host generates sub-populations with distinct phenotypes

Helicobacter pylori chronically infects the stomach of approximately half of the worlds population. Manifestation of clinical diseases associated with H. pylori infection, including cancer, is driven by strain properties and host responses; and as chronic infection persists, both are subject to change. Previous studies have documented frequent and extensive within-host bacterial genetic variation. To define how within-host diversity contributes to phenotypes related to H. pylori pathogenesis, this project leverages a collection of 39 clinical isolates acquired prospectively from a single subject at two time points and from multiple gastric sites. During the six years separating collection of these isolates, this individual, initially harboring a duodenal ulcer, progressed to gastric atrophy and concomitant loss of acid secretion. Whole genome sequence analysis identified 2,232 unique single nucleotide polymorphisms (SNPs) across isolates and a nucleotide substitution rate of 1.3x10-4 substitutions/site/year. Gene ontology analysis identified cell envelope genes among the genes with excess accumulation of nonsynonymous SNPs (nSNPs). A dendrogram based on genetic similarity, clusters isolates from each time point separately. Within time points, there is segregation of subgroups with phenotypic differences in bacterial morphology, ability to induce inflammatory cytokines, and mouse colonization. Higher inflammatory cytokine induction in recent isolates maps to shared polymorphisms in the Cag PAI protein, CagY, while rod morphology in a subgroup of recent isolates mapped to eight mutations in three distinct helical cell shape determining (csd) genes. The presence of subgroups with unique genetic and phenotypic properties suggest complex selective forces and multiple sub-niches within the stomach during chronic infection. Author SummaryHelicobacter pylori, one of the most common bacterial pathogens colonizing humans, is the main agent responsible for stomach ulcers and cancer. Certain strain types are associated with increased risk of disease, however many factors contributing to disease outcome remain unknown. Prior work has documented genetic diversity among bacterial populations within single individuals, but the impact of this diversity for continued bacterial infection or disease progression remains understudied. In our analysis we examined both genetic and functional features of many stomach isolates from a single individual infected over six years. During these six years the subject shifted from having excess acid production and a duodenal ulcer to lower acid production from gastric atrophy. The 39 isolates form sub-populations based on gene sequence changes that accumulated in the different isolates. In addition to having distinguishing genetic features, these sub-populations also have differences in several bacterial properties, including cell shape, ability to activate immune responses, and colonization in a mouse model of infection. This apparent functional specialization suggests that the bacterial sub-populations may have adapted to distinct sub-niches within the stomach during chronic infection.

microbiology↗

bioRxiv2019

MACS: A Novel Concept for High-Magnification Imaging of Stretch-Activated Cells Reveals Divergent Nuclear Behavior to Different Levels of Strain

Mechanical cues from the environment influence cell behavior. Mechanisms of cellular mechanosensation are unclear, partially due to a lack of methods that can reveal dynamic processes. Here, we present a new concept for a low-cost, 3D-printed TENSCell (TENSion in Cells) device, that enables high-magnification imaging of cells during stretch. Using this device, we observed that nuclei of mouse embryonic skin fibroblasts underwent rapid and divergent responses, characterized by nuclear area expansion during 5% strain, but nuclear area shrinkage during 20% strain. Only responses to low strain were dependent on calcium signaling, while actin inhibition abrogated all nuclear responses and increased nuclear strain transfer and DNA damage. Imaging of actin dynamics during stretch revealed similar divergent trends, with F-actin shifting away from (5% strain) or towards (20% strain) the nuclear periphery. Our findings emphasize the importance of simultaneous stimulation and data acquisition to capture rapid mechanosensitive processes and suggest that mechanical confinement of nuclei through actin may be a protective mechanism during high strain loads.\n\nSTATEMENT OF SIGNIFICANCECells can sense and respond to mechanical cues in their environment. These responses can be rapid, on the time scale of seconds, and new methods are required for their acquisition and study. We introduce a new concept for a 3D-printed cell-stretch device that allows for simultaneous high-resolution imaging, while also being low-cost and easy to assemble to enable broad applicability. Using this device, we further demonstrated to importance of simultaneous stimulation and data acquisition to elicit mechanosensitive cell behavior as we observed rapid changes in nuclear size and reorganization of actin filaments around the nuclear border in skin cells. Overall, our results suggest that the rapid reorganization of actin during high loads might protect the genome from strain-induced damage.

cell biology↗

bioRxiv2018

The Nucleus Mediates Mechanosensitive Reorganization of Epigenetically Marked Chromatin During Cardiac Maturation and Pathology

Environmental mechanical cues are critical to guide cell fate. Forces transmit to the nucleus through the Linker of Nucleo- and Cytoskeleton (LINC) complex and are thought to influence the organization of chromatin that is related to cell differentiation; however, the underlying mechanisms are unclear. Here, we investigated chromatin reorganization during murine cardiac development and found that cardiomyocytes establish a distinct architecture characterized by relocation of H3K9me3-modified chromatin from the nuclear interior to the periphery and co-localization to myofibrils. This effect was abrogated in stiff environments that inhibited cardiomyocyte contractility, or after LINC complex disruption, and resulted in the relocation of H3K27me3-modified chromatin instead. By generating high-resolution intra-nuclear strain maps during cardiomyocyte contraction, we discovered that the reorganization of H3K9me3-marked chromatin is influenced by tensile, but not compressive, nuclear strains. Our findings highlight a new role for nuclear mechanosensation in guiding cell fate through chromatin reorganization in response to environmental cues.

cell biology↗