Extracellular Matrix Function Research Articles

Bioactive and chemically defined hydrogels with tunable stiffness guide cerebral organoid formation and modulate multi-omics plasticity in cerebral organoids.

Organoids are an emerging technology with great potential in human disease modelling, drug development, diagnosis, tissue engineering, and regenerative medicine. Organoids as 3D-tissue culture systems have gained special attention in the past decades due to their ability to faithfully recapitulate the complexity of organ-specific tissues. Despite considerable successes in culturing physiologically relevant organoids, their real-life applications are currently limited by challenges such as scarcity of an appropriate biomimetic matrix. Peptide amphiphiles (PAs) due to their well-defined chemistry, tunable bioactivity, and extracellular matrix (ECM)-like nanofibrous architecture represent an attractive material scaffold for organoids development. Using cerebral organoids (COs) as exemplar, we demonstrate the possibility to create bio-instructive hydrogels with tunable stiffness ranging from 0.69kPa to 2.24kPa to culture and induce COs growth. We used orthogonal chemistry involving oxidative coupling and supramolecular interactions to create two-component hydrogels integrating the bio-instructive activity and ECM-like nanofibrous architecture of a laminin-mimetic PAs (IKVAV-PA) and tunable crosslinking density of hyaluronic acid functionalized with tyramine (HA-Try). Multi-omics technology including transcriptomics, proteomics, and metabolomics reveals the induction and growth of COs in soft HA-Tyr hydrogels containing PA-IKVAV such that the COs display morphology and biomolecular signatures similar to those grown in Matrigel scaffolds. Our materials hold great promise as a safe synthetic ECM for COs induction and growth. Our approach represents a well-defined alternative to animal-derived matrices for the culture of COs and might expand the applicability of organoids in basic and clinical research. STATEMENT OF SIGNIFICANCE: Synthetic bio-instructive materials which display tissue-specific functionality and nanoscale architecture of the native extracellular matrix are attractive matrices for organoids development. These synthetic matrices are chemically defined and animal-free compared to current gold standard matrices such as Matrigel. Here, we developed hydrogel matrices with tunable stiffness, which incorporate laminin-mimetic peptide amphiphiles to grow and expand cerebral organoids. Using multi-omics tools, the present study provides exciting data on the effects of neuro-inductive cues on the biomolecular profiles of brain organoids.

Decellularized Extracellular Matrix Retards Premature Senescence of Human Endometrial Mesenchymal Stromal Cells

The extracellular matrix (ECM), the main component of the extracellular space, mediates signaling between cells and controls the key cell functions—proliferation, differentiation, and migration. The relevance of studying ECM is due to a wide range of its biological properties that can be applied in regenerative medicine and bioengineering. Cell-derived decellularized ECM (dECM) is used to study ECM as a regulator of the cell functional activity, as well as to mimic their tissue-specific microenvironment. Here, we hypothesized that dECM deposited by Wharton’s jelly-derived MSCs modulates the senescence phenotype of endometrial MSCs (eMSCs) acquired in response to oxidative stress. This aspect of ECM functioning in the context of eMSCs has so far remained unexplored. A comparative study of prolonged H2O2-induced senescence of eMSCs exposed to both dECM and cultured plastic showed that dECM may effectively downregulate the main senescence markers. Our findings suggest that ECM is able to partially reverse (retard) the eMSCs premature senescence.

Guiding the Path to Healing: CuO2 -Laden Nanocomposite Membrane for Diabetic Wound Treatment.

Diabetic chronic wounds pose significant clinical challenges due to their characteristic features of impaired extracellular matrix (ECM) function, diminished angiogenesis, chronic inflammation, and increased susceptibility to infection. To tackle these challenges and provide a comprehensive therapeutic approach for diabetic wounds,the first coaxial electrospun nanocomposite membrane isdeveloped that incorporates multifunctional copper peroxide nanoparticles (n-CuO2 ). The membrane's nanofiber possesses a unique "core/sheath" structure consisting of n-CuO2 +PVP (Polyvinylpyrrolidone)/PCL (Polycaprolactone) composite sheath and a PCL core. When exposed to the wound's moist environment, PVP within the sheath gradually disintegrates, releasing the embedded n-CuO2 . Under a weakly acidic microenvironment (typically diabetic and infected wounds), n-CuO2 decomposes to release H2 O2 and Cu2+ ions and subsequently produce ·OH through chemodynamic reactions. This enables the anti-bacterial activity mediated by reactive oxygen species (ROS), suppressing the inflammation while enhancing angiogenesis. At the same time, the dissolution of PVP unveils unique nano-grooved surface patterns on the nanofibers, providing desirable cell-guiding function required for accelerated skin regeneration. Through meticulous material selection and design, this study pioneers the development of functional nanocomposites for multi-modal wound therapy, which holds great promise in guiding the path to healing for diabetic wounds.

An overview of extracellular matrix and its remodeling in the development of cancer and metastasis with a glance at therapeutic approaches.

The extracellular matrix (ECM) is an inevitable part of tissues able to provide structural support for cells depending on the purpose of tissues and organs. The dynamic characteristics of ECM let this system fluently interact with the extrinsic triggers and get stiffed, remodeled, and/or degraded ending in maintaining tissue homeostasis. ECM could serve as the platform for cancer progression. The dysregulation of biochemical and biomechanical ECM features might take participate in some pathological conditions such as aging, tissue destruction, fibrosis, and particularly cancer. Tumors can reprogram how ECM remodels by producing factors able to induce protein synthesis, matrix proteinase expression, degradation of the basement membrane, growth signals and proliferation, angiogenesis, and metastasis. Therefore, targeting the ECM components, their secretion, and their interactions with other cells or tumors could be a promising strategy in cancer therapies. The present study initially introduces the physiological functions of ECM and then discusses how tumor-dependent dysregulation of ECM could facilitate cancer progression and ends with reviewing the novel therapeutic strategies regarding ECM.

Postnatal development of extracellular matrix and vascular function in small arteries of the rat.

Introduction: Vascular extracellular matrix (ECM) is dominated by elastic fibers (elastin with fibrillin-rich microfibrils) and collagens. Current understanding of ECM protein development largely comes from studies of conduit vessels (e.g., aorta) while resistance vessel data are sparse. With an emphasis on elastin, we examined whether changes in postnatal expression of arteriolar wall ECM would correlate with development of local vasoregulatory mechanisms such as the myogenic response and endothelium-dependent dilation. Methods: Rat cerebral and mesenteric arteries were isolated at ages 3, 7, 11, 14, 19days, 2months, and 2years. Using qPCR mRNA expression patterns were examined for elastin, collagen types I, II, III, IV, fibrillin-1, and -2, lysyl oxidase (LOX), and transglutaminase 2. Results: Elastin, LOX and fibrillar collagens I and III mRNA peaked at day 11-14 in both vasculatures before declining at later time-points. 3D confocal imaging for elastin showed continuous remodeling in the adventitia and the internal elastic lamina for both cerebral and mesenteric vessels. Myogenic responsiveness in cannulated cerebral arteries was detectable at day 3 with constriction shifted to higher intraluminal pressures by day 19. Myogenic responsiveness of mesenteric vessels appeared fully developed by day 3. Functional studies were performed to investigate developmental changes in endothelial-dependent dilation. Endothelial-dependent dilation to acetylcholine was less at day 3 compared to day 19 and at day 3 lacked an endothelial-derived hyperpolarizing factor component that was evident at day 19. Conclusion: Collectively, in the rat small artery structural remodeling and aspects of functional control continue to develop in the immediate postnatal period.

Extracellular matrix in synovium development, homeostasis and arthritis disease

Extracellular matrix (ECM) is a three-dimensional network entity composed of extracellular macromolecules. ECM in synovium not only supports the structural integrity of synovium, but also plays a crucial role in regulating homeostasis and damage repair response in synovium. Obvious disorders in the composition, behavior and function of synovial ECM will lead to the occurrence and development of arthritis diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and psoriatic arthritis (PsA). Based on the importance of synovial ECM, targeted regulation of the composition and structure of ECM is considered to be an effective measure for the treatment of arthritis disease. This paper reviews the current research status of synovial ECM biology, discusses the role and mechanism of synovial ECM in physiological status and arthritis disease, and summarizes the current strategies for targeting synovial ECM to provide information for the pathogenesis, diagnosis and treatment of arthritis disease.

Quantitative proteomic analysis of cattle-yak and yak longissimus thoracis provides insights into the differential mechanisms of meat quality

In this study, proteins of cattle-yak longissimus thoracis (CYLT) and yak longissimus thoracis (YLT) were compared using tandem mass tag-labeled quantitative proteomic analysis. A total of 157 proteins were screened as differentially abundant proteins (DAPs) derived from 1551 quantitative proteins. Bioinformatics analysis revealed that the upregulated DAPs in CYLT were mainly involved in energy metabolism, oxidative stress, muscle fiber structure, and extracellular matrix (ECM), while the downregulated DAPs were mainly involved in energy metabolism and ECM function. The upregulated myoglobin, downregulation of NADH dehydrogenase, and upregulation of cytochrome oxidase indicated that CYLT initiates compensatory regulation in response to hypoxic high-altitude environments. Two differentially abundant myosins and five collagens suggested that CYLT and YLT may have distinct differences in the assembly structure of muscle fibers and connective tissue. These differences in energy metabolism and muscle structure will inevitably affect the postmortem physiology of “muscle to meat” and consequently the meat qualities. Therefore, our results will provide important clues to gain insight into the potential causes of meat quality differences between cattle-yak and yak based on high-altitude response.

Investigating material basis and molecular mechanism of Qing Cuo formula in the treatment of acne based on animal experiments, UPLC-LTQ-Orbitrap-MS and network pharmacology

Context Qing Cuo Formula (QCF) is a traditional Chinese medicine for treating acne, but its active compounds and molecular mechanisms are unclear. Objective To investigate the material basis and molecular mechanism of QCF. Materials and methods In vivo experiments were conducted on 60 male golden hamsters with damp-heat acne, with a blank group, a spironolactone group and 3 QCF administration groups (given high, medium and low doses) over a 30-day period. Serum androgen and inflammatory cytokine levels were tested by ELISA. In vitro, chemical compositions of QCF were investigated by UPLC-LTQ-Orbitrap-MS. Network pharmacology approaches were used to analyse the protein–protein interaction (PPI) network and QCF active compounds-intersection targets-acne network. GO enrichment and KEGG pathway analysis was conducted subsequently. Results Low-dose QCF group (11.4 g/kg/day) showed significantly reduced levels of serum T (4.94 ± 0.36; 5.51 ± 0.36 ng/mL), DHT (6.67 ± 0.61; 8.09 ± 0.59 nmol/L), E2 (209.01 ± 20.92; 237.08 ± 13.94 pg/mL), IL-1α (36.84 ± 3.23; 44.07 ± 4.00 pg/mL) and FFA (128.32 ± 10.94; 148.00 ± 12.12 µmol/L) compared to the blank group (p < 0.05). In vitro experiments identified 75 compounds in QCF decoction, with 27 active compounds absorbed in serum. Network pharmacology identified 6 active components connecting 17 targets. GO enrichment and KEGG pathway analysis indicated that QCF’s anti-acne targets mainly regulate extracellular matrix function, inflammatory processes, immune response and endocrine function. Conclusions This study provides evidence of the molecular mechanism and material basis of QCF in treating androgen-related damp-heat acne, paving the way for further research on its potential in treating other conditions related to damp-heat constitution.

Loss of the extracellular matrix protein Perlecan disrupts axonal and synaptic stability during Drosophila development.

Heparan sulfate proteoglycans (HSPGs) form essential components of the extracellular matrix (ECM) and basement membrane (BM) and have both structural and signaling roles. Perlecan is a secreted ECM-localized HSPG that contributes to tissue integrity and cell-cell communication. Although a core component of the ECM, the role of Perlecan in neuronal structure and function is less understood. Here, we identify a role for Drosophila Perlecan in the maintenance of larval motoneuron axonal and synaptic stability. Loss of Perlecan causes alterations in the axonal cytoskeleton, followed by axonal breakage and synaptic retraction of neuromuscular junctions. These phenotypes are not prevented by blocking Wallerian degeneration and are independent of Perlecan's role in Wingless signaling. Expression of Perlecan solely in motoneurons cannot rescue synaptic retraction phenotypes. Similarly, removing Perlecan specifically from neurons, glia, or muscle does not cause synaptic retraction, indicating the protein is secreted from multiple cell types and functions non-cell autonomously. Within the peripheral nervous system, Perlecan predominantly localizes to the neural lamella, a specialized ECM surrounding nerve bundles. Indeed, the neural lamella is disrupted in the absence of Perlecan, with axons occasionally exiting their usual boundary in the nerve bundle. In addition, entire nerve bundles degenerate in a temporally coordinated manner across individual hemi-segments throughout larval development. These observations indicate disruption of neural lamella ECM function triggers axonal destabilization and synaptic retraction of motoneurons, revealing a role for Perlecan in axonal and synaptic integrity during nervous system development.

Loss of the extracellular matrix protein Perlecan disrupts axonal and synaptic stability during Drosophila development

Heparan sulfate proteoglycans (HSPGs) form essential components of the extracellular matrix (ECM) and basement membrane (BM) and have both structural and signaling roles. Perlecan is a secreted ECM-localized HSPG that contributes to tissue integrity and cell-cell communication. Although a core component of the ECM, the role of Perlecan in neuronal structure and function is less understood. Here, we identify a role for Drosophila Perlecan in the maintenance of larval motoneuron axonal and synaptic stability. Loss of Perlecan causes alterations in the axonal cytoskeleton, followed by axonal breakage and synaptic retraction of neuromuscular junctions. These phenotypes are not prevented by blocking Wallerian degeneration and are independent of Perlecan’s role in Wingless signaling. Expression of Perlecan solely in motoneurons cannot rescue synaptic retraction phenotypes. Similarly, removing Perlecan specifically from neurons, glia, or muscle does not cause synaptic retraction, indicating the protein is secreted from multiple cell types and functions non-cell autonomously. Within the peripheral nervous system, Perlecan predominantly localizes to the neural lamella, a specialized ECM surrounding nerve bundles. Indeed, the neural lamella is disrupted in the absence of Perlecan, with axons occasionally exiting their usual boundary in the nerve bundle. In addition, entire nerve bundles degenerate in a temporally coordinated manner across individual hemi-segments throughout larval development. These observations indicate disruption of neural lamella ECM function triggers axonal destabilization and synaptic retraction of motoneurons, revealing a role for Perlecan in axonal and synaptic integrity during nervous system development.

NHR-23 activity is necessary for C. elegans developmental progression and apical extracellular matrix structure and function.

Nematode molting is a remarkable process where animals must repeatedly build a new apical extracellular matrix (aECM) beneath a previously built aECM that is subsequently shed. The nuclear hormone receptor NHR-23 (also known as NR1F1) is an important regulator of C. elegans molting. NHR-23 expression oscillates in the epidermal epithelium, and soma-specific NHR-23 depletion causes severe developmental delay and death. Tissue-specific RNAi suggests that nhr-23 acts primarily in seam and hypodermal cells. NHR-23 coordinates the expression of factors involved in molting, lipid transport/metabolism and remodeling of the aECM. NHR-23 depletion causes dampened expression of a nas-37 promoter reporter and a loss of reporter oscillation. The cuticle collagen ROL-6 and zona pellucida protein NOAH-1 display aberrant annular localization and severe disorganization over the seam cells after NHR-23 depletion, while the expression of the adult-specific cuticle collagen BLI-1 is diminished and frequently found in patches. Consistent with these localization defects, the cuticle barrier is severely compromised when NHR-23 is depleted. Together, this work provides insight into how NHR-23 acts in the seam and hypodermal cells to coordinate aECM regeneration during development.

A Cholangiocarcinoma Prediction Model Based on Random Forest and Artificial Neural Network Algorithm.

To construct a prognostic model using artificial neural network (ANN) approach, providing an idea for the prediction and diagnosis of cholangiocarcinoma (CCA). Experimental study. Place and Duration of the Study: Department of General Surgery, Zhenjiang Hospital, Zhenjiang Province, China, between January and March 2022. Available datasets were obtained from the Gene Expression Omnibus (GEO) database to construct the train cohort and the test cohort of CCA, and screened out the differentially expressed genes (DEGs) of CCA. Next, an ANN model for CCA diagnosis was constructed based on the scores of the DEGs and evaluated its accuracy and efficiency using ROC curves. Finally, the immune infiltration and the function of extracellular matrix (ECM) protein SPACRL1 were analysed to reveal the characteristic alterations in CCA. This analysis revealed 166 DEGs, mainly concentrated in the ECM organisation, neutrophil activation and other pathways. Then a set of 17 CCA disease signature genes scores were obtained to build an ANN prediction model and the ROC curve was plotted. The AUC in the train group (0.980) indicated that the accuracy of the diagnosis model is extremely high. Finally, there was a significant increase of B cells naïve (p=0.025), tregs (p=0.004), and macrophages M1 (p<0.001) in the tumour-microenvironment of CCA, while SPARCL1 was a protective factor on disease-specific survival (DSS) in CCA (p=0.009). This study has developed an accurate prediction model for CCA diagnosis, and identified SPARCL1 as pivotal factor in CCA by modulating the tumour immune-microenvironment. Cholangiocarcinoma, Artificial neural network, Immune microenvironment, Bioinformatics, Prognosis model, SPARCL1.

A self-assembled dynamic extracellular matrix-like hydrogel system with multi-scale structures for cell bioengineering applications

Extracellular matrix (ECM) provides various types of direct interactions with cells and a dynamic environment, which can be remodeled through different assembly/degradation mechanisms to adapt to different biological processes. Herein, through introducing polyphosphate-modified hyaluronic acid and bioactive glass (BG) nano-fibril into a self-assembled hydrogel system with peptide-polymer conjugate, we can realize many new ECM-like functions in a synthetic polymer network. The hydrogel network formation is mediated by coacervation, followed by a gradual transition of peptide structure from α-helix to β-sheet. The ECM-like hydrogels can be degraded through a number of orthogonal mechanisms, including treatments with protease, hyaluronidase, alkaline phosphatase, and calcium ion. As 2D coating, the ECM-like hydrogels can be used to modify the planar surface to promote the adhesion of mesenchymal stromal cells, or to coat the cell surface in a layer-by-layer fashion to shield the interaction with the substrate. As ECM-like hydrogels for 3D cell culture, the system is compatible with injection and cell encapsulation. Upon incorporating fragmented electrospun bioactive glass nano-fibril into the hydrogels, the synergetic effects of soft hydrogel and stiff reinforcement nanofibers on recapitulating ECM functions result in reduced cell circularity in 3D. Finally, by injecting the ECM-like hydrogels into mice, gradual degradations over a time period of one month and high biocompatibility have been shown in vivo. The contribution of complex network dynamics and hierarchical structures to cell-biomatrix interaction can be investigated multi-dimensionally, as many mechanisms are orthogonal to each other and can be regulated individually. STATEMENT OF SIGNIFICANCE: A list of native ECM features has attracted the most interest and attention in the research of synthetic biomaterials. In this research, we have described a simple ECM-like hydrogel system in which the complex and elegant functions of native ECM can be recapitulated in a chemically defined synthetic system. The ECM-like hydrogel systems were developed to avoid undesired features of biological substances (e.g., ethical concerns, batch-to-batch variation, immunogenicity, and potential risk of contamination), as well as gaining new functions to facilitate bioengineering applications (e.g., 3D cell culture, injection, and high stability). To this end, we have developed an ECM-like hydrogel system and provide evidence that this purely synthetic biomaterial is a promising candidate for cell bioengineering applications.

Upregulation of extracellular proteins in a mouse model of Alzheimer’s disease

Various risk factors of Alzheimer’s disease (AD) are known, such as advanced age, possession of certain genetic variants, accumulation of toxic amyloid-β (Aβ) peptides, and unhealthy lifestyle. An estimate of heritability of AD ranges from 0.13 to 0.25, indicating that its phenotypic variation is accounted for mostly by non-genetic factors. DNA methylation is regarded as an epigenetic mechanism that interfaces the genome with non-genetic factors. The Tg2576 mouse model has been insightful in AD research. These transgenic mice express a mutant form of human amyloid precursor protein linked to familial AD. At 9–13 months of age, these mice show elevated levels of Aβ peptides and cognitive impairment. The current literature lacks integrative multiomics of the animal model. We applied transcriptomics and DNA methylomics to the same brain samples from ~ 11-month-old transgenic mice. We found that genes involved in extracellular matrix structures and functions are transcriptionally upregulated, and genes involved in extracellular protein secretion and localization are differentially methylated in the transgenic mice. Integrative analysis found enrichment of GO terms related to memory and synaptic functionability. Our results indicate a possibility of transcriptional modulation by DNA methylation underlying AD neuropathology.

CEBPD is a master transcriptional factor for hypoxia regulated proteins in glioblastoma and augments hypoxia induced invasion through extracellular matrix-integrin mediated EGFR/PI3K pathway

Hypoxia contributes to the initiation and progression of glioblastoma by regulating a cohort of genes called hypoxia-regulated genes (HRGs) which form a complex molecular interacting network (HRG-MINW). Transcription factors (TFs) often play central roles for MINW. The key TFs for hypoxia induced reactions were explored using proteomic analysis to identify a set of hypoxia-regulated proteins (HRPs) in GBM cells. Next, systematic TF analysis identified CEBPD as a top TF that regulates the greatest number of HRPs and HRGs. Clinical sample and public database analysis revealed that CEBPD is significantly up-regulated in GBM, high levels of CEBPD predict poor prognosis. In addition, CEBPD is highly expressed in hypoxic condition both in GBM tissue and cell lines. For molecular mechanisms, HIF1α and HIF2α can activate the CEBPD promotor. In vitro and in vivo experiments demonstrated that CEBPD knockdown impaired the invasion and growth capacity of GBM cells, especially in hypoxia condition. Next, proteomic analysis identified that CEBPD target proteins are mainly involved in the EGFR/PI3K pathway and extracellular matrix (ECM) functions. WB assays revealed that CEBPD significantly positively regulated EGFR/PI3K pathway. Chromatin immunoprecipitation (ChIP) qPCR/Seq analysis and Luciferase reporter assay demonstrated that CEBPD binds and activates the promotor of a key ECM protein FN1 (fibronectin). In addition, the interactions of FN1 and its integrin receptors are necessary for CEBPD-induced EGFR/PI3K activation by promoting EGFR phosphorylation. Furthermore, GBM sample analysis in the database corroborated that CEBPD is positively correlated with the pathway activities of EGFR/PI3K and HIF1α, especially in highly hypoxic samples. At last, HRPs are also enriched in ECM proteins, indicating that ECM activities are important components of hypoxia induced responses in GBM. In conclusion, CEPBD plays important regulatory roles in the GBM HRG-MINW as a key TF, which activates the EGFR/PI3K pathway through ECM, especially FN1, mediated EGFR phosphorylation.

Enhanced wound-healing efficacy of electrospun mesoporous hydroxyapatite nanoparticle-loaded chitosan nanofiber developed using pluronic F127

One of the goals of wound repairing is to mimic the function and architecture of the native extracellular matrix (ECM). To this end, for the first time, we used pluronic F127 and mesoporous rod-like hydroxyapatite nanoparticles (mr-HAP NPs) simultaneously to prepare a novel low-diameter electrospun ECM-mimicking wound dressing based on a mixture of chitosan and polyethylene oxide. F127 is used as a surface tension regulator of the polymer solution. In addition, F127 has the special ability to reduce the size of nanofibers. mr-HAP NPs are used as cell proliferation accelerators which also improve the mechanical properties and water uptake capacity of the as-prepared dressing. The average size of nanofibers in the presence of F127 was about 110 nm which was more than 2.5 times lower than nanofibers prepared without F127. The water uptake capacity was evaluated to investigate the wound exudate absorption capacity of the wound dressing. It was observed that the incorporation of mr-HAP NPs into wound dressing structure increases the water uptake capacity by more than 2.5 times. Alongside the evaluation of cytocompatibility through in vitro cell viability assay, the wound healing efficacy was also determined in full-thickness skin wounds in a rat model for 15 days. The cytocompatible wound dressing showed significantly higher wound closure efficacy than the control group so the wounds healed entirely on the last day of the treatment period. As well, the pathology analysis proved better granulation tissue development and greater re-epithelialization. These findings are by virtue of the improved mechanical properties, accelerated cell migration and proliferation, proper environment for oxygen exchange, and enhanced exudate uptake of the wound dressing. These all are due to the presence of F127 and mr-HAP.

Independent control over cell patterning and adhesion on hydrogel substrates for tissue interface mechanobiology

Tissue boundaries and interfaces are engines of morphogenesis invivo. However, despite a wealth of micropatterning approaches available to control tissue size, shape, and mechanical environment invitro, fine-scale spatial control of cell positioning within tissue constructs remains an engineering challenge. To address this, we augment DNA "velcro" technology for selective patterning of ssDNA-labeled cells on mechanically defined photoactive polyacrylamide hydrogels. Hydrogels bearing photopatterned single-stranded DNA (ssDNA) features for cell capture are then co-functionalized with extracellular matrix (ECM) proteins to support subsequent adhesion of patterned tissues. ECM protein co-functionalization does not alter ssDNA pattern fidelity, cell capture, or hydrogel elastic stiffness. This approach enables mechanobiology studies and measurements of signaling activity at dynamic cell interfaces with precise initial patterning. Combining DNA velcro patterning and ECM functionalization provides independent control of initial cell placement, adhesion, and mechanics, constituting a new tool for studying biological interfaces and for programming multicellular interactions in engineered tissues.

Impact of trace elements and risk factor for glaucoma pathogenesis

Abstract Glaucoma is a multifunctional disease with several trace elements associated with its pathophysiology. This review aimed to provide readers with a sound and scientific understanding of the risk factors related to the pathogenicity of the disease. This review covers the aspects of investigating trace element risk factors associated with glaucomatous pathogenesis from a fundamental biomechanical point of view. A study of a significant amount of literature suggests that several trace element elements are associated with intraocular pressure (IOP), trabecular meshwork, and optical nerve oxidative stress changes in complex eye diseases. Traces such as selenium, chromium, manganese, magnesium, iron, cobalt, copper, and zinc elements are significantly associated with primary open-angle glaucoma (POAG). Other risk factors, such as trace elements, modulate opposing aqueous humor production and outflow dynamics, extracellular matrix structure and function, and neurotransmitter release. The current evidence and human expertise help us understand that our diet contains numerous factors that may influence optically dynamic parameters, such as IOP and drug outcome effectiveness.

Passing the post: roles of posttranslational modifications in the form and function of extracellular matrix.

The extracellular matrix (ECM) is central to the physiology of animal tissues, through its multifaceted roles in tissue structure, mechanical properties, and cell interactions, and by its cell-signaling activities that regulate cell phenotype and behavior. The secretion of ECM proteins typically involves multiple transport and processing steps within the endoplasmic reticulum and the subsequent compartments of the secretory pathway. Many ECM proteins are substituted with various posttranslational modifications (PTMs) and there is increasing evidence of how PTM additions are required for ECM protein secretion or functionality within the extracellular milieu. The targeting of PTM-addition steps may thus offer opportunities to manipulate ECM quality or quantity, in vitro or in vivo. This review discusses selected examples of PTMs of ECM proteins for which the PTM has known importance for anterograde trafficking and secretion of the core protein, and/or loss-of-function of the respectively modifying enzyme leads to alterations of ECM structure or function with pathophysiological consequences in humans. Members of the protein disulfide isomerase (PDI) family have central roles in disulfide bond formation and isomerization within the endoplasmic reticulum, and are discussed in relation to emerging knowledge of the roles of certain PDIs in ECM production in the pathophysiological context of breast cancer. Cumulative data suggest the possible applicability of inhibition of PDIA3 activity to modulate ECM composition and functionality within the tumor microenvironment.

The factory, the antenna and the scaffold: the three-way interplay between the Golgi, cilium and extracellular matrix underlying tissue function.

The growth and development of healthy tissues is dependent on the construction of a highly specialised extracellular matrix (ECM) to provide support for cell growth and migration and to determine the biomechanical properties of the tissue. These scaffolds are composed of extensively glycosylated proteins which are secreted and assembled into well-ordered structures that can hydrate, mineralise, and store growth factors as required. The proteolytic processing and glycosylation of ECM components is vital to their function. These modifications are under the control of the Golgi apparatus, an intracellular factory hosting spatially organised, protein-modifying enzymes. Regulation also requires a cellular antenna, the cilium, which integrates extracellular growth signals and mechanical cues to inform ECM production. Consequently, mutations in either Golgi or ciliary genes frequently lead to connective tissue disorders. The individual importance of each of these organelles to ECM function is well-studied. However, emerging evidence points towards a more tightly linked system of interdependence between the Golgi, cilium and ECM. This review examines how the interplay between all three compartments underpins healthy tissue. As an example, it will look at several members of the golgin family of Golgi-resident proteins whose loss is detrimental to connective tissue function. This perspective will be important for many future studies looking to dissect the cause and effect of mutations impacting tissue integrity.