scholarly journals Nanomechanical mechanisms of Lyme disease spirochete motility enhancement in extracellular matrix

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Martin Strnad ◽  
Yoo Jin Oh ◽  
Marie Vancová ◽  
Lisa Hain ◽  
Jemiina Salo ◽  
...  

AbstractAs opposed to pathogens passively circulating in the body fluids of their host, pathogenic species within the Spirochetes phylum are able to actively coordinate their movement in the host to cause systemic infections. Based on the unique morphology and high motility of spirochetes, we hypothesized that their surface adhesive molecules might be suitably adapted to aid in their dissemination strategies. Designing a system that mimics natural environmental signals, which many spirochetes face during their infectious cycle, we observed that a subset of their surface proteins, particularly Decorin binding protein (Dbp) A/B, can strongly enhance the motility of spirochetes in the extracellular matrix of the host. Using single-molecule force spectroscopy, we disentangled the mechanistic details of DbpA/B and decorin/laminin interactions. Our results show that spirochetes are able to leverage a wide variety of adhesion strategies through force-tuning transient molecular binding to extracellular matrix components, which concertedly enhance spirochetal dissemination through the host.

Development ◽  
1991 ◽  
Vol 111 (3) ◽  
pp. 667-681 ◽  
Author(s):  
P.Y. Goh ◽  
T. Bogaert

As part of a general study of genes specifying a pattern of muscle attachments, we identified and genetically characterised mutants in the mup-1 gene. The body wall muscles of early stage mup-1 embryos have a wild-type myofilament pattern but may extend ectopic processes. Later in embryogenesis, some body wall muscles detach from the hypodermis. Genetic analysis suggests that mup-1 has both a maternal and a zygotic component and is not required for postembryonic muscle growth and attachment. mup-1 mutants are suppressed by mutations in several genes that encode extracellular matrix components. We propose that mup-1 may encode a cell surface/extracellular matrix molecule required both for the positioning of body wall muscle attachments in early embryogenesis and the subsequent maintenance of these attachments to the hypodermis until after cuticle synthesis.


2020 ◽  
Vol 77 (12) ◽  
pp. 3831-3841
Author(s):  
Lidia Muscariello ◽  
Barbara De Siena ◽  
Rosangela Marasco

AbstractThe gut microbiota is a complex microbial ecosystem where bacteria, through mutual interactions, cooperate in maintaining of wellbeing and health. Lactobacilli are among the most important constituents of human and animal intestinal microbiota and include many probiotic strains. Their presence ensures protection from invasion of pathogens, as well as stimulation of the immune system and protection of the intestinal flora, often exerted through the ability to interact with mucus and extracellular matrix components. The main factors responsible for mediating adhesion of pathogens and commensals to the gut are cell surface proteins that recognize host targets, as mucus layer and extracellular matrix proteins. In the last years, several adhesins have been reported to be involved in lactobacilli–host interaction often miming the same mechanism used by pathogens.


2020 ◽  
Vol 295 (29) ◽  
pp. 10008-10022 ◽  
Author(s):  
Giampiero Pietrocola ◽  
Angelica Pellegrini ◽  
Mariangela J. Alfeo ◽  
Loredana Marchese ◽  
Timothy J. Foster ◽  
...  

Staphylococcus aureus is an important bacterial pathogen that can cause a wide spectrum of diseases in humans and other animals. S. aureus expresses a variety of virulence factors that promote infection with this pathogen. These include cell-surface proteins that mediate adherence of the bacterial cells to host extracellular matrix components, such as fibronectin and fibrinogen. Here, using immunoblotting, ELISA, and surface plasmon resonance analysis, we report that the iron-regulated surface determinant B (IsdB) protein, besides being involved in heme transport, plays a novel role as a receptor for the plasma and extracellular matrix protein vitronectin (Vn). Vn-binding activity was expressed by staphylococcal strains grown under iron starvation conditions when Isd proteins are expressed. Recombinant IsdB bound Vn dose dependently and specifically. Both near-iron transporter motifs NEAT1 and NEAT2 of IsdB individually bound Vn in a saturable manner, with KD values in the range of 16–18 nm. Binding of Vn to IsdB was specifically blocked by heparin and reduced at high ionic strength. Furthermore, IsdB-expressing bacterial cells bound significantly higher amounts of Vn from human plasma than did an isdB mutant. Adherence to and invasion of epithelial and endothelial cells by IsdB-expressing S. aureus cells was promoted by Vn, and an αvβ3 integrin-blocking mAb or cilengitide inhibited adherence and invasion by staphylococci, suggesting that Vn acts as a bridge between IsdB and host αvβ3 integrin.


2021 ◽  
pp. 088532822110543
Author(s):  
Nisa İrem Büyük ◽  
Kardelen Tüfekçi ◽  
Alev Cumbul ◽  
Erhan Ayşan ◽  
Gamze Torun Köse

This study aimed to generate a novel biomatrix from the decellularized human parathyroid capsule using different methods and to compare the efficiency of decellularization in the means of cell removal, structural integrity and extracellular matrix preservation. The parathyroid capsules, which were carefully dissected from the parathyroid tissue, were randomly divided into four groups and then decellularized using three different protocols: freeze-thaw only, sodium dodecyl sulphate and Triton X-100 treatments after freeze-thawing. Quantitative DNA analysis, agarose gel electrophoresis, sulphated glycosaminoglycan assay, histological analysis, immunohistochemistry and scanning electron microscopy were used to observe the efficiency of parathyroid capsule decellularization and preservation of extracellular matrix components. Considering all the results, it can be said that only freeze-thawing is not an effective method in parathyroid capsule decellularization. When the tissue was treated with a detergent agent in addition to freeze-thawing, the amount of DNA decreased by 90% while sulphated glycosaminoglycan amount maintained 50% compared to untreated tissue. Comparing the effects of the two detergents on the preservation of extracellular matrix such as collagen and sulphated glycosaminoglycan, it was seen that the integrity of tissues treated with Triton X-100 was preserved more than tissues treated with sodium dodecyl sulphate. It is concluded that Triton X-100 treatment with freeze-thawing is the most suitable and effective method for decellularizing the human parathyroid capsule. The biomatrix obtained with this method can be applied in the transplantation of parathyroid tissue and other endocrine tissue types in the body.


Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 18-20
Author(s):  
Shuhei Tsuchiya

Osseointegration can be defined as a direct connection, both structural and functional, between living bone and the surface of an artificial implant. Indeed, the word comes from the Greek term for 'bone' and 'to make whole'. In dentistry, once dental implants are placed, the body will react with osseointegration, enabling the implants to become a permanent part of the jaw. There are many benefits to this type of implant, compared with traditional tooth replacement options, not least that dental implants mimic the strength and functionality of a natural tooth. Dr Shuhei Tsuchiya is a researcher based in the Division of Oral and Maxillofacial Surgery at Nagoya University, Japan, who is interested in a range of areas, including regenerative medicine and the extracellular matrix. One of his key preoccupations, though, is shedding light on osseointegration. He and his team are working to unravel the mysteries of the mechanism.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.


2021 ◽  
Vol 714 (3) ◽  
pp. 032023
Author(s):  
Ling Chen ◽  
Liya Yang ◽  
Chunxia Wang ◽  
Ting Zhu

2021 ◽  
Vol 7 ◽  
pp. 205951312098032
Author(s):  
Chenyu Huang ◽  
Rei Ogawa

Introduction: Keloids are pathological scars that are notorious for their chronic and relentless invasion into adjacent healthy skin, with commonly seen post-therapeutic recurrence after monotherapies. Methods: An English literature review on keloid pathophysiology was performed by searching the PubMed, Embase and Web of Science databases, to find out the up-to-date relevant articles. The level of evidence was evaluated based on the included studies with the highest level of evidence first. Results: Keloid morphology, signs, symptoms and the histopathological changes that occur in the local cells and extracellular matrix components are described. The theories on the pathophysiology of keloidogenesis that have been proposed to date are also covered; these include endocrinological, nutritional, vascular, and autoimmunological factors. In addition, we describe the local mechanical forces (and the mechanosignalling pathways by which these forces shape keloid cell activities) that promote keloid formation and determine the direction of invasion of keloids and the body sites that are prone to them. Conclusion: A better understanding of this pathological entity, particularly its mechanobiology, will aid the development of new diagnostic and therapeutic strategies for use in the clinic to prevent, reduce or even reverse the growth of this pathological scar. Lay Summary Keloids are skin scars that are famous for their chronic invasion into healthy skin, with commonly seen recurrence after surgeries. Cells such as lymphocytes, macrophages, mast cells and endothelial cells are involved in keloid growth. Particularly, endocrinological, nutritional, vascular, autoimmunological and mechanical factors actively take part in keloid progression.


Sign in / Sign up

Export Citation Format

Share Document