Graduate Student The Pennsylvania State University, United States
Introduction:: The human colon is home to more than a trillion microorganisms that modulate diverse gastrointestinal processes and pathophysiologies. Our understanding of how this gut ecosystem impacts human health, although rapidly evolving, is still in its nascent stages and has been slowed by the lack of accessible and scalable tools suitable to studying complex host-mucus-microbe interactions. In this work, we report a synthetic gel-like material capable of recapitulating the varied structural, mechanical and biochemical profiles of native human colonic mucus.
Materials and Methods:: The viscous fibrillar material is realized through the templated assembly of a fluorine-rich amino acid at liquid-liquid phase separated interfaces. The fluorine-assisted mucus surrogate (FAMS) can be decorated with various mucins to serve as a habitat for microbial colonization and integrated with human colorectal epithelial cells to generate multicellular artificial mucosae.
Results, Conclusions, and Discussions:: FAMS are generated from the interfacial organization of the non-natural amino acid pentafluorophenyalanine at fluorous-water interphases to form a viscous, double layer, colloid. This hybrid architecture of fibrillar and coacervate assemblies was found to closely mimic the structure and mechanical performance of native colonic mucus. We demonstrate this synthetic platform can be readily coated with a variety of mucin proteins, support the colonization of gastrointestinal commensals, and be directly incorporated with colorectal epithelial cells to create customizable ex vivo microbiome organoids (see Figure). This establishes a synthetic mucus analogue with independently tailorable mechanical, structural, and biochemical properties to allow for the creation of designer multicellular systems amenable to high throughput applications. As an exemplary demonstration, we incorporate these materials into a gastrointestinal permeability assay and demonstrate their ability to model oral bioavailability of macromolecular compounds.
