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PloS One 2022Woody cells, such as tracheids, fibers, vessels, rays etc., have unique structural characteristics such as nano-scale ultrastructure represented by multilayers,...
Woody cells, such as tracheids, fibers, vessels, rays etc., have unique structural characteristics such as nano-scale ultrastructure represented by multilayers, microfibril angle (MFA), micro-scale anatomical properties and spatial arrangement. Simultaneous evaluation of the above indices is very important for their adequate quantification and extracting the effects of external stimuli from them. However, it is difficult in general to achieve the above only by traditional methodologies. To overcome the above point, a new methodological framework combining polarization optical microscopy, fluorescence microscopy, and image segmentation is proposed. The framework was tested to a model softwood species, Chamaecyparis obtusa for characterizing intra-annual transition of MFA and tracheid morphology in a radial file unit. According our result, this framework successfully traced the both characteristics tracheid by tracheid and revealed the high correlation (|r| > 0.5) between S2 microfibril angles and tracheidal morphology (lumen radial diameter, tangential wall thickness and cell wall occupancy). In addition, radial file based evaluation firstly revealed their complex transitional behavior in transition and latewood. The proposed framework has great potential as one of the unique tools to provide detailed insights into heterogeneity of intra and inter-cells in the wide field of view through the simultaneous evaluation of cells' ultrastructure and morphological properties.
Topics: Microfibrils; Microscopy; Wood; Cell Wall; Chamaecyparis
PubMed: 36378676
DOI: 10.1371/journal.pone.0277616 -
Planta Sep 2022TEM and AFM imaging reveal radial orientations and whorl-like arrangements of cellulose microfibrils near the S1/S2 interface. These are explained by wrinkling during...
TEM and AFM imaging reveal radial orientations and whorl-like arrangements of cellulose microfibrils near the S1/S2 interface. These are explained by wrinkling during lamellar cell growth. In the most widely accepted model of the ultrastructure of wood cell walls, the cellulose microfibrils are arranged in helical patterns on concentric layers. However, this model is contradicted by a number of transmission electron microscopy (TEM) studies which reveal a radial component to the microfibril orientations in the cell wall. The idea of a radial component of the microfibril directions is not widely accepted, since it cannot easily be explained within the current understanding of lamellar cell growth. To help clarify the microfibril arrangements in wood cell walls, we have investigated various wood cell wall sections using both transmission electron microscopy and atomic force microscopy, and using various imaging and specimen preparation methods. Our investigations confirm that the microfibrils have a radial component near the interface between the S1 and S2 cell wall layers, and also reveal a whorl-like microfibril arrangement at the S1/S2 interface. These whorl-like structures are consistent with cell wall wrinkling during growth, allowing the radial microfibril component to be reconciled with the established models for lamellar cell growth.
Topics: Cell Wall; Cellulose; Microfibrils; Microscopy, Atomic Force; Wood
PubMed: 36087126
DOI: 10.1007/s00425-022-03976-2 -
Cellular and Molecular Life Sciences :... Oct 2011Tissue microfibrils contain fibrillin-1 as a major constituent. Microfibrils regulate bioavailability of TGFβ superfamily growth factors and are structurally crucial in... (Review)
Review
Tissue microfibrils contain fibrillin-1 as a major constituent. Microfibrils regulate bioavailability of TGFβ superfamily growth factors and are structurally crucial in the ocular zonule. FBN1 mutations typically cause the Marfan syndrome, an autosomal dominant disorder manifesting with skeletal overgrowth, aortic aneurysm, and lens dislocation (ectopia lentis). Infrequently, FBN1 mutations cause dominantly inherited Weill-Marchesani syndrome (WMS), isolated ectopia lentis (IEL), or the fibrotic condition, geleophysic dysplasia (GD). Intriguingly, mutations in ADAMTS [a disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif] family members phenocopy these disorders, leading to recessive WMS (ADAMTS10), WMS-like syndrome (ADAMTS17), IEL (ADAMTSL4 and ADAMTS17) and GD (ADAMTSL2). An ADAMTSL2 founder mutation causes Musladin-Lueke syndrome, a fibrotic disorder in beagle dogs. The overlapping disease spectra resulting from fibrillin-1 and ADAMTS mutations, interaction of ADAMTS10 and ADAMTSL2 with fibrillin-1, and evidence that these ADAMTS proteins accelerate microfibril biogenesis, constitutes a consilience suggesting that some ADAMTS proteins evolved to provide a novel mechanism regulating microfibril formation and consequently cell behavior.
Topics: ADAM Proteins; Amino Acid Motifs; Animals; Binding Sites; Dogs; Extracellular Matrix; Fibrillin-1; Fibrillins; Humans; Marfan Syndrome; Metalloendopeptidases; Mice; Microfibrils; Microfilament Proteins; Multigene Family; Mutation; Thrombospondins; Transforming Growth Factor beta
PubMed: 21858451
DOI: 10.1007/s00018-011-0780-9 -
Oncogene Jun 2023Highly desmoplastic and immunosuppressive tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) contributes to tumor progression and resistance to...
Highly desmoplastic and immunosuppressive tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) contributes to tumor progression and resistance to current therapies. Clues targeting the notorious stromal environment have offered hope for improving therapeutic response whereas the underlying mechanism remains unclear. Here, we find that prognostic microfibril associated protein 5 (MFAP5) is involved in activation of cancer-associated fibroblasts (CAFs). Inhibition of MFAP5CAFs shows synergistic effect with gemcitabine-based chemotherapy and PD-L1-based immunotherapy. Mechanistically, MFAP5 deficiency in CAFs downregulates HAS2 and CXCL10 via MFAP5/RCN2/ERK/STAT1 axis, leading to angiogenesis, hyaluronic acid (HA) and collagens deposition reduction, cytotoxic T cells infiltration, and tumor cells apoptosis. Additionally, in vivo blockade of CXCL10 with AMG487 could partially reverse the pro-tumor effect from MFAP5 overexpression in CAFs and synergize with anti-PD-L1 antibody to enhance the immunotherapeutic effect. Therefore, targeting MFAP5CAFs might be a potential adjuvant therapy to enhance the immunochemotherapy effect in PDAC via remodeling the desmoplastic and immunosuppressive microenvironment.
Topics: Humans; Cancer-Associated Fibroblasts; Microfibrils; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Proteins; Immunotherapy; Tumor Microenvironment; Calcium-Binding Proteins
PubMed: 37156839
DOI: 10.1038/s41388-023-02711-9 -
Frontiers in Cell and Developmental... 2023Fibrillin-1 (FBN1) is a large, cysteine-rich, calcium binding extracellular matrix glycoprotein encoded by gene. It serves as a structural component of microfibrils and... (Review)
Review
Fibrillin-1 (FBN1) is a large, cysteine-rich, calcium binding extracellular matrix glycoprotein encoded by gene. It serves as a structural component of microfibrils and provides force-bearing mechanical support in elastic and nonelastic connective tissue. As such, mutations in the gene can cause a wide variety of genetic diseases such as Marfan syndrome, an autosomal dominant disorder characterized by ocular, skeletal and cardiovascular abnormalities. FBN1 also interacts with numerous microfibril-associated proteins, growth factors and cell membrane receptors, thereby mediating a wide range of biological processes such as cell survival, proliferation, migration and differentiation. Dysregulation of FBN1 is involved in the pathogenesis of many human diseases, such as cancers, cardiovascular disorders and kidney diseases. Paradoxically, both depletion and overexpression of FBN1 upregulate the bioavailability and signal transduction of TGF-β via distinct mechanisms in different settings. In this review, we summarize the structure and expression of FBN1 and present our current understanding of the functional role of FBN1 in various human diseases. This knowledge will allow to develop better strategies for therapeutic intervention of FBN1 related diseases.
PubMed: 38269088
DOI: 10.3389/fcell.2023.1302285 -
International Journal of Molecular... Jul 2022The self-assembly process of β-D-glucose oligomers on the surface of cellulose Iβ microfibril involves crystallization, and this process is analyzed herein, in terms...
The self-assembly process of β-D-glucose oligomers on the surface of cellulose Iβ microfibril involves crystallization, and this process is analyzed herein, in terms of the length and flexibility of the oligomer chain, by means of molecular dynamics (MD) simulations. The characterization of this process involves the structural relaxation of the oligomer, the recognition of the cellulose I microfibril, and the formation of several hydrogen bonds (HBs). This process is monitored on the basis of the changes in non-bonded energies and the interaction with hydrophilic and hydrophobic crystal faces. The oligomer length is considered a parameter for capturing insight into the energy landscape and its stability in the bound form with the cellulose I microfibril. We notice that the oligomer-microfibril complexes are more stable by increasing the number of hydrogen bond interactions, which is consistent with a gain in electrostatic energy. Our studies highlight the interaction with hydrophilic crystal planes on the microfibril and the acceptor role of the flexible oligomers in HB formation. In addition, we study by MD simulation the interaction between a protofibril and the cellulose I microfibril in solution. In this case, the main interaction consists of the formation of hydrogen bonds between hydrophilic faces, and those HBs involve donor groups in the protofibril.
Topics: Cellulose; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Microfibrils; Molecular Dynamics Simulation
PubMed: 35955639
DOI: 10.3390/ijms23158505 -
Seminars in Cell & Developmental Biology May 2019Fibrillin microfibrils are extensible polymers that endow connective tissues with long-range elasticity and have widespread distributions in both elastic and non-elastic... (Review)
Review
Fibrillin microfibrils are extensible polymers that endow connective tissues with long-range elasticity and have widespread distributions in both elastic and non-elastic tissues. They act as a template for elastin deposition during elastic fibre formation and are essential for maintaining the integrity of tissues such as blood vessels, lung, skin and ocular ligaments. A reduction in fibrillin is seen in tissues in vascular ageing, chronic obstructive pulmonary disease, skin ageing and UV induced skin damage, and age-related vision deterioration. Most mutations in fibrillin cause Marfan syndrome, a genetic disease characterised by overgrowth of the long bones and other skeletal abnormalities with cardiovascular and eye defects. However, mutations in fibrillin and fibrillin-binding proteins can also cause short-stature pathologies. All of these diseases have been linked to dysregulated growth factor signalling which forms a major functional role for fibrillin.
Topics: Animals; Elastic Tissue; Elasticity; Elastin; Extracellular Matrix Proteins; Fibrillins; Humans; Intercellular Signaling Peptides and Proteins; Microfibrils; Microfilament Proteins; Signal Transduction; Skin
PubMed: 30016650
DOI: 10.1016/j.semcdb.2018.07.016 -
Cancer Medicine Apr 2023Distant metastasis is the main cause of mortality in colorectal cancer (CRC) patients. N1-methyladenosine (m1A) is a type of epitranscriptome modification. While its...
BACKGROUND
Distant metastasis is the main cause of mortality in colorectal cancer (CRC) patients. N1-methyladenosine (m1A) is a type of epitranscriptome modification. While its regulatory effect on mRNA and its role in CRC metastasis remain unclear.
METHODS
The m1A methylation profile of mRNAs in CRC was revealed by m1A methylated RNA immunoprecipitation sequencing. The expression of MFAP2 in tumor tissues was measured by immunohistochemistry and then correlated with the clinical characteristics and prognosis of CRC patients. The role of MFAP2 in the invasiveness of CRC cells was evaluated by transwell assays and peritoneal metastatic model in nude mice. The downstream targets of MFAP2 was screened by mass spectrometry analysis. Then the role of MFAP2-CLK3 signaling axis was verified by cotransfecting MFAP2 siRNA and CLK3 plasmid in CRC cells.
RESULTS
Microfibril associated protein 2 (MFAP2) mRNA was overexpressed and m1A-hypermethylated in CRC. High expression of MFAP2 was closely related to lymph node metastasis and distant metastasis, leading to poor prognosis in patients with CRC. In vivo and in vitro studies showed that silencing of MFAP2 inhibited the migration, invasion and metastasis of CRC cells. CDC Like Kinase 3 (CLK3) was a potential downstream target of MFAP2. Further studies showed that MFAP2 depletion might induce autophagic degradation of CLK3, and the role of MFAP2 in the invasiveness of CRC cells was dependent on CLK3.
CONCLUSIONS
Our results uncover a newly identified MFAP2-CLK3 signaling axis, which is a potential therapeutic target for CRC metastasis.
Topics: Animals; Mice; Cell Line, Tumor; Methylation; Mice, Nude; Microfibrils; Colorectal Neoplasms; Proteins; Cell Proliferation; Neoplasm Invasiveness; Gene Expression Regulation, Neoplastic; Cell Movement
PubMed: 36583532
DOI: 10.1002/cam4.5561 -
International Journal of Molecular... Jan 2022Elastin represents the structural component of the extracellular matrix providing elastic recoil to tissues such as skin, blood vessels and lungs. Elastogenic cells... (Review)
Review
Elastin represents the structural component of the extracellular matrix providing elastic recoil to tissues such as skin, blood vessels and lungs. Elastogenic cells secrete soluble tropoelastin monomers into the extracellular space where these monomers associate with other matrix proteins (e.g., microfibrils and glycoproteins) and are crosslinked by lysyl oxidase to form insoluble fibres. Once elastic fibres are formed, they are very stable, highly resistant to degradation and have an almost negligible turnover. However, there are circumstances, mainly related to inflammatory conditions, where increased proteolytic degradation of elastic fibres may lead to consequences of major clinical relevance. In severely affected COVID-19 patients, for instance, the massive recruitment and activation of neutrophils is responsible for the profuse release of elastases and other proteolytic enzymes which cause the irreversible degradation of elastic fibres. Within the lungs, destruction of the elastic network may lead to the permanent impairment of pulmonary function, thus suggesting that elastases can be a promising target to preserve the elastic component in COVID-19 patients. Moreover, intrinsic and extrinsic factors additionally contributing to damaging the elastic component and to increasing the spread and severity of SARS-CoV-2 infection are reviewed.
Topics: Animals; COVID-19; Elastic Tissue; Elastin; Extracellular Matrix; Extracellular Matrix Proteins; Extracellular Traps; Fibrillins; Humans; Lung; Microfibrils; Microfilament Proteins; Neutrophils; Protein-Lysine 6-Oxidase; SARS-CoV-2; Tropoelastin
PubMed: 35163482
DOI: 10.3390/ijms23031559 -
Frontiers in Plant Science 2020Plants use rigid cellulose together with non-cellulosic matrix polymers to build cell walls. Cellulose microfibrils comprise linear β(1,4)-glucan chains packed through...
Plants use rigid cellulose together with non-cellulosic matrix polymers to build cell walls. Cellulose microfibrils comprise linear β(1,4)-glucan chains packed through inter- and intra-chain hydrogen-bonding networks and van der Waals forces. Due to its small size, the number of glucan chains and their arrangement in a microfibril remains elusive. Here we used atomic force microscopy (AFM) to directly image primary cell walls (PCWs) and secondary cell walls (SCWs) from fresh tissues of maize () under near-native conditions. By analyzing cellulose structure in different types of cell walls, we were able to measure the individual microfibrils in elongated PCWs at the sub-nanometer scale. The dimension of the microfibril was measured at 3.68 ± 0.13 nm in width and 2.25 ± 0.10 nm in height. By superimposing multiple AFM height profiles of these microfibrils, the overlay area representing the cross-section was estimated at 5.6 ± 0.4 nm, which fitted well to an 18-chain model packed as six sheets with 234432 conformation. Interestingly we found in PCW, all these individual microfibrils could be traced back to a bundle in larger imaging area, suggesting cellulose are synthesized as large bundles in PCWs, and then split during cell expansion or elongation. In SCWs where cell growth has ceased we observed nearly-parallel twined or individual microfibrils that appeared to be embedded separately in the matrix polymers without the splitting effect, indicating different mechanisms of cellulose biosynthesis in PCW and SCW. The sub-nanometer structure of the microfibril presented here was measured exclusively from elongated PCWs, further study is required to verify if it represents the inherent structure synthesized by the cellulose synthase complex in PCWs and SCWs.
PubMed: 32391038
DOI: 10.3389/fpls.2020.00479