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Crouzier, Thomas
Publications (5 of 5) Show all publications
Petrou, G., Jansson, R., Högqvist, M., Hedhammar, M. & Crouzier, T. (2018). Engineering mucoadhesive silk. Paper presented at 255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA. Abstracts of Papers of the American Chemical Society, 255
Open this publication in new window or tab >>Engineering mucoadhesive silk
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2018 (English)In: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-240166 (URN)000435537701238 ()
Conference
255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA
Note

OC 20190110

Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-05-10Bibliographically approved
Petrou, G., Jansson, R., Hogqvist, M., Erlandsson, J., Wågberg, L., Hedhammar, M. & Crouzier, T. (2018). Genetically Engineered Mucoadhesive Spider Silk. Biomacromolecules, 19(8), 3268-3279
Open this publication in new window or tab >>Genetically Engineered Mucoadhesive Spider Silk
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2018 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, no 8, p. 3268-3279Article in journal (Refereed) Published
Abstract [en]

Mucoadhesion is defined as the adhesion of a material to the mucus gel covering the mucous membranes. The mechanisms controlling mucoadhesion include nonspecific electrostatic interactions and specific interactions between the materials and the mucins, the heavily glycosylated proteins that form the mucus gel. Mucoadhesive materials can be used to develop mucosal wound dressings and noninvasive transmucosal drug delivery systems. Spider silk, which is strong, biocompatible, biodegradable, nontoxic, and lightweight would serve as an excellent base for the development of such materials. Here, we investigated two variants of the partial spider silk protein 4RepCT genetically engineered in order to functionalize them with mucoadhesive properties. The pLys-4RepCT variant was functionalized with six cationically charged lysines, aiming to provide nonspecific adhesion from electrostatic interactions with the anionically charged mucins, while the hGal3-4RepCT variant was genetically fused with the Human Galectin-3 Carbohydrate Recognition Domain which specifically binds the mucin glycans Gal beta 1-3GlcNAc and Gal beta 1-4GlcNAc. First, we demonstrated that coatings, fibers, meshes, and foams can be readily made from both silk variants. Measured by the adsorption of both bovine submaxillary mucin and pig gastric mucin, the newly produced silk materials showed enhanced mucin binding properties compared with materials of wild-type (4RepCT) silk. Moreover, we showed that pLys-4RepCT silk coatings bind mucins through electrostatic interactions, while hGal3-4RepCT silk coatings bind mucins through specific glycan-protein interactions. We envision that the two new mucoadhesive silk variants pLys-4RepCT and hGal3-4RepCT, alone or combined with other biofunctional silk proteins, constitute useful new building blocks for a range of silk protein-based materials for mucosal treatments.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:kth:diva-234195 (URN)10.1021/acs.biomac.8b00578 (DOI)000441852400011 ()29932649 (PubMedID)2-s2.0-85049259614 (Scopus ID)
Note

QC 20180920

Available from: 2018-09-20 Created: 2018-09-20 Last updated: 2019-04-13Bibliographically approved
Petrou, G. & Crouzier, T. (2018). Mucins as multifunctional building blocks of biomaterials. Biomaterials Science, 6(9), 2282-2297
Open this publication in new window or tab >>Mucins as multifunctional building blocks of biomaterials
2018 (English)In: Biomaterials Science, ISSN 2047-4830, E-ISSN 2047-4849, Vol. 6, no 9, p. 2282-2297Article, review/survey (Refereed) Published
Abstract [en]

Mucins are large glycoproteins that are ubiquitous in the animal kingdom. Mucins coat the surfaces of many cell types and can be secreted to form mucus gels that assume important physiological roles in many animals. Our growing understanding of the structure and function of mucin molecules and their functionalities has sparked interest in investigating the use of mucins as building blocks for innovative functional biomaterials. These pioneering studies have explored how new biomaterials can benefit from the barrier properties, hydration and lubrication properties, unique chemical diversity, and bioactivities of mucins. Owing to their multifunctionality, mucins have been used in a wide variety of applications, including as antifouling coatings, as selective filters, and artificial tears and saliva, as basis for cosmetics, as drug delivery materials, and as natural detergents. In this review, we summarize the current knowledge regarding key mucin properties and survey how they have been put to use. We offer a vision for how mucins could be used in the near future and what challenges await the field before biomaterials made of mucins and mucin-mimics can be translated into commercial products.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-235116 (URN)10.1039/c8bm00471d (DOI)000443267300001 ()30047553 (PubMedID)2-s2.0-85052118759 (Scopus ID)
Note

QC 20180917

Available from: 2018-09-17 Created: 2018-09-17 Last updated: 2018-09-17Bibliographically approved
Kootala, S., Filho, L., Srivastava, V., Linderberg, V., Moussa, A., David, L., . . . Crouzier, T. (2018). Reinforcing Mucus Barrier Properties with Low Molar Mass Chitosans. Biomacromolecules, 19(3), 872-882
Open this publication in new window or tab >>Reinforcing Mucus Barrier Properties with Low Molar Mass Chitosans
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2018 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, no 3, p. 872-882Article in journal (Refereed) Published
Abstract [en]

The mucus gel covers the wet epithelia that forms the inner lining of the body. It constitutes our first line of defense protecting the body from infections and other deleterious molecules. Failure of the mucus barrier can lead to the inflammation of the mucosa such as in inflammatory bowel diseases. Unfortunately, there are no effective strategies that reinforce the mucus barrier properties to recover or enhance its ability to protect the epithelium. Herein, we describe a mucus engineering approach that addresses this issue where we physically cross-link the mucus gel with low molar mass chitosan variants to reinforce its barrier functions. We tested the effect of these chitosans on mucus using in-lab purified porcine gastric mucins, which mimic the native properties of mucus, and on mucus-secreting HT29-MTX epithelial cell cultures. We found that the lowest molar mass chitosan variant (degree of polymerization of 8) diffuses deep into the mucus gels while physically cross-linking the mucin polymers, whereas the higher molar mass chitosan variants (degree of polymerization of 52 and 100) interact only superficially. The complexation resulted in a tighter mucin polymer mesh that slowed the diffusion of dextran polymers and of the cholera toxin B subunit protein through the mucus gels. These results uncover a new use for low molar mass mucoadhesive polymers such as chitosans as noncytotoxic mucosal barrier enhancers that could be valuable in the prevention and treatment of mucosal diseases.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-224590 (URN)10.1021/acs.biomac.7b01670 (DOI)000427539600017 ()29451983 (PubMedID)2-s2.0-85043581772 (Scopus ID)
Funder
Swedish Research Council, 2014-6203
Note

QC 20180320

Available from: 2018-03-20 Created: 2018-03-20 Last updated: 2018-04-05Bibliographically approved
Yan, H., Chircov, C., Zhong, X., Winkeljann, B., Dobryden, I., Nilsson, H. E., . . . Crouzier, T. (2018). Reversible Condensation of Mucins into Nanoparticles. Langmuir, 34(45), 13615-13625
Open this publication in new window or tab >>Reversible Condensation of Mucins into Nanoparticles
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2018 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 34, no 45, p. 13615-13625Article in journal (Refereed) Published
Abstract [en]

Mucins are high molar mass glycoproteins that assume an extended conformation and can assemble into mucus hydrogels that protect our mucosal epithelium. In nature, the challenging task of generating a mucus layer, several hundreds of micrometers in thickness, from micrometer-sized cells is elegantly solved by the condensation of mucins inside vesicles and their on-demand release from the cells where they suddenly expand to form the extracellular mucus hydrogel. We aimed to recreate and control the process of compaction for mucins, the first step toward a better understanding of the process and creating biomimetic in vivo delivery strategies of macromolecules. We found that by adding glycerol to the aqueous solvent, we could induce drastic condensation of purified mucin molecules, reducing their size by an order of magnitude down to tens of nanometers in diameter. The condensation effect of glycerol was fully reversible and could be further enhanced and partially stabilized by cationic cross-linkers such as calcium and polylysine. The change of structure of mucins from extended molecules to nano-sized particles in the presence of glycerol translated into macroscopic rheological changes, as illustrated by a dampened shear-thinning effect with increasing glycerol concentration. This work provides new insight into mucin condensation, which could lead to new delivery strategies mimicking cell release of macromolecules condensed in vesicles such as mucins and heparin.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-239774 (URN)10.1021/acs.langmuir.8b02190 (DOI)000450695000018 ()30350704 (PubMedID)2-s2.0-85056360596 (Scopus ID)
Note

QC 20190109

Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-01-09Bibliographically approved
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