skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Comparative mucomic analysis of three functionally distinct Cornu aspersum Secretions
Abstract Every animal secretes mucus, placing them among the most diverse biological materials. Mucus hydrogels are complex mixtures of water, ions, carbohydrates, and proteins. Uncertainty surrounding their composition and how interactions between components contribute to mucus function complicates efforts to exploit their properties. There is substantial interest in commercializing mucus from the garden snail,Cornu aspersum, for skincare, drug delivery, tissue engineering, and composite materials.C. aspersumsecretes three mucus—one shielding the animal from environmental threats, one adhesive mucus from the pedal surface of the foot, and another pedal mucus that is lubricating. It remains a mystery how compositional differences account for their substantially different properties. Here, we characterize mucus proteins, glycosylation, ion content, and mechanical properties that could be used to provide insight into structure-function relationships through an integrative “mucomics” approach. We identify macromolecular components of these hydrogels, including a previously unreported protein class termed Conserved Anterior Mollusk Proteins (CAMPs). Revealing differences betweenC. aspersummucus shows how considering structure at all levels can inform the design of mucus-inspired materials.  more » « less
Award ID(s):
1933525
PAR ID:
10505557
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
Springer Nature
Date Published:
Journal Name:
Nature Communications
Volume:
14
Issue:
1
ISSN:
2041-1723
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Rotifers possess complex morphologies despite their microscopic size and simple appearance. Part of this complexity is hidden in the structure of their organs, which may be cellular or syncytial. Surprisingly, organs that are cellular in one taxon can be syncytial in another. Pedal glands are widespread across Rotifera and function in substrate attachment and/or egg brooding. These glands are normally absent inAsplanchna, which lack feet and toes that function as outlets for pedal glandular secretions in other rotifers. Here, we describe the ultrastructure of a pedal gland that is singular and syncytial inAsplanchnaaff.herricki, but is normally paired and cellular in all other rotifers.Asplanchnaaff.herrickihas a single large pedal gland that is active and secretory; it has a bipartite, binucleate, syncytial body and a cytosol filled with rough endoplasmic reticulum, Golgi, and several types of secretory vesicles. The most abundant vesicle type is large and contains a spherical electron‐dense secretion that appears to be produced through homotypic fusion of condensing vesicles produced by the Golgi. The vesicles appear to undergo a phase transition from condensed to decondensed along their pathway toward the gland lumen. Decondensation changes the contents to a mucin‐like matrix that is eventually exocytosed in a “kiss‐and‐run” fashion with the plasma membrane of the gland lumen. Exocytosed mucus enters the gland lumen and exits through an epithelial duct that is an extension of the syncytial integument. This results in mucus that extends from the rotifer as a long string as the animal swims through the water. The function of this mucus is unknown, but we speculate it may function in temporary attachment, prey capture, or floatation. 
    more » « less
  2. Abstract Prior work suggests influenza A virus (IAV) crosses the airway mucus barrier in a sialic acid‐dependent manner through the actions of the viral envelope proteins, hemagglutinin, and neuraminidase. However, host and viral factors that influence how efficiently mucus traps IAV remain poorly defined. In this work, how the physicochemical properties of mucus influence its ability to effectively capture IAV is assessed using fluorescence video microscopy and multiple particle tracking. Our studies suggest an airway mucus gel layer must be produced with virus‐sized pores to physically constrain IAV. While sialic acid binding by IAV may improve mucus trapping efficiency, sialic acid binding preference is found to have little impact on IAV mobility and the fraction of viral particles expected to penetrate the mucus barrier. Further, synthetic polymeric hydrogels engineered with mucus‐like architecture are similarly protective against IAV infection despite their lack of sialic acid decoy receptors. Together, this work provides new insights on mucus barrier function toward IAV with important implications on innate host defense and transmission of respiratory viruses. 
    more » « less
  3. Atack, John M. (Ed.)
    ABSTRACT Mucins are glycoproteins which can be found in host cell membranes and as a gelatinous surface formed from secreted mucins. Mucosal surfaces in mammals form a barrier to invasive microbes, particularly bacteria, but are a point of attachment for others.Clostridioides difficileis an anaerobic bacterium, which colonizes the mammalian gastrointestinal (GI) tract and is a common cause of acute GI inflammation leading to a variety of negative outcomes. AlthoughC. difficiletoxicity stems from secreted toxins, colonization is a prerequisite forC. difficiledisease. WhileC. difficileis known to associate with the mucous layer and underlying epithelium, the mechanisms underlying these interactions that facilitate colonization are less well understood. To understand the molecular mechanisms by whichC. difficileinteracts with mucins, we usedex vivomucosal surfaces to test the ability ofC. difficileto bind to mucins from different mammalian tissues. We found significant differences inC. difficileadhesion based upon the source of mucins, with highest levels of binding observed to mucins purified from the human colonic adenocarcinoma line LS174T and lowest levels of binding to porcine gastric mucin. We also observed defects in adhesion by mutants deficient in flagella but not type IV pili. These results imply that interactions between host mucins andC. difficileflagella facilitate the initial host attachment ofC. difficileto host cells and secreted mucus. IMPORTANCEClostridioides difficileis one of the leading causes of hospital-acquired infections worldwide and presents challenges in treatment due to recurrent gastrointestinal disease after treatment with antimicrobials. The mechanisms by whichC. difficilecolonizes the gut represent a key gap in knowledge, including its association with host cells and mucosa. Our results show the importance of flagellin for specific adhesion to mucosal hydrogels and can help to explain prior observations of adhesive defects in flagellin and pilin mutants. 
    more » « less
  4. Abstract Shear‐recoverable hydrogels based on block copolypeptides with rapid self‐recovery hold potential in extrudable and injectable 3D‐printing applications. In this work, a series of 3‐arm star‐shaped block copolypeptides composed of an inner hydrophilic poly(l‐glutamate) domain and an outer β‐sheet forming domain is synthesized with varying side chains and block lengths. By changing the β‐sheet forming domains, hydrogels with diverse microstructures and mechanical properties are prepared and structure–function relationships are determined using scattering and rheological techniques. Differences in the properties of these materials are amplified during direct‐ink writing with a strong correlation observed between printability and material chemistry. Significantly, it is observed that non‐canonical β‐sheet blocks based on phenyl glycine form more stable networks with superior mechanical properties and writability compared to widely used natural amino acid counterparts. The versatile design available through block copolypeptide materials provides a robust platform to access tunable material properties based solely on molecular design. These systems can be exploited in extrusion‐based applications such as 3D‐printing without the need for additives. 
    more » « less
  5. Abstract Two related classes of ligand-binding hemec-containing proteins with a high degree of structural homology have been identified and characterized over recent decades: cytochromes P460 (cyts P460), defined by an unusual heme-lysine cross-link, and cytochromesc′-β (cytsc′-β), containing a canonicalc-heme without the lysine cross-link. The shared protein fold of the cyt P460-cytc′-β superfamily can accommodate a variety of heme environments with entirely different reactivities. On the one hand, cyts P460 with polar distal pockets have been shown to oxidize NH2OH to NO and/or N2O via proton-coupled electron transfer. On the other hand, cytsc′-β with hydrophobic distal pockets have a proposed gas binding function similar to the unrelated, but more extensively characterized, alpha helical cytochromesc′. Recent studies have also identified ‘halfway house’ proteins (cyts P460 with non-polar heme pockets and cytsc′-β with polar distal heme pockets) with functions yet to be resolved. Here, we review the structural, spectroscopic and enzymatic properties of the cyt P460-cytc′-β superfamily with a view to understanding the structural determinants of their different functional properties. Graphical abstract 
    more » « less