Characterization of an engineered mucus microenvironment for in vitro modeling of host–microbe interactions

Andy J. Huang, Courtney L. O’Brien, Nicholas Dawe, Anas Tahir, Alison J. Scott, Brendan M. Leung

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

10 Citas (Scopus)

Resumen

The human mucus layer plays a vital role in maintaining health by providing a physical barrier to pathogens. This biological hydrogel also provides the microenvironment for commensal bacteria. Common models used to study host–microbe interactions include gnotobiotic animals or mammalian–microbial co-culture platforms. Many of the current in vitro models lack a sufficient mucus layer to host these interactions. In this study, we engineered a mucus-like hydrogel Consisting of a mixed alginate-mucin (ALG-MUC) hydrogel network by using low concentration calcium chloride (CaCl2) as crosslinker. We demonstrated that the incorporation of ALG-MUC hydrogels into an aqueous two-phase system (ATPS) co-culture platform can support the growth of a mammalian monolayer and pathogenic bacteria. The ALG-MUC hydrogels displayed selective diffusivity against macromolecules and stability with ATPS microbial patterning. Additionally, we showed that the presence of mucin within hydrogels contributed to an increase in antimicrobial resistance in ATPS patterned microbial colonies. By using common laboratory chemicals to generate a mammalian–microbial co-culture system containing a representative mucus microenvironment, this model can be readily adopted by typical life science laboratories to study host–microbe interaction and drug discovery.

Idioma originalEnglish
Número de artículo5515
PublicaciónScientific Reports
Volumen12
N.º1
DOI
EstadoPublished - dic. 2022

Nota bibliográfica

Funding Information:
This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (RGPIN-2018-05742; RGPIN-2021-02401) and the Canadian Foundation for Innovation John R. Evans Leaders Fund. CO is supported by a Scotia Scholar Award from Research Nova Scotia. ND is supported by the Canadian Graduate Scholarship (NSERC), the Dalhousie Medical Research Foundation Genomics in Medicine Scholarship and the Helyer/Williams Studentship through the Beatrice Hunter Cancer Research Institute.

Funding Information:
The authors would like to thank Dr. Andrew Stadnyk and Dr. Elizabeth Cowley in the Department of Microbiology and Immunology (Dalhousie University) and the Department of Physiology and Biophysics (Dalhousie University), respectively, for providing the mammalian cell lines used. We also thank Dr. Zhenyu Cheng, in the Department of Microbiology and Immunology (Dalhousie University), for providing the bacterial strains used in this study. We are also grateful for Dr. Kevin Plucknett and Dr. Gianfranco Mazzanti in the Department of Mechanical Engineering (Dalhousie University) and the Department of Process Engineering and Applied Science (Dalhousie University), respectively, for access to the rheometer.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus Subject Areas

  • General

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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