Biology subjects

Arias, S. L.

Publications and source records attributed to Arias, S. L..

4 recordsLinked to original sources

bioRxiv2025

Environmental factors drive bacterial degradation of gastrointestinal mucus

The mucus layer lining the gastrointestinal tract is essential for gut health, providing a protective barrier against pathogens while maintaining symbiosis with the microbiome. Its disruption is a hallmark of gastrointestinal diseases like ulcerative colitis. While glycan foraging by gut bacteria is thought to initiate mucus disruption, its impact on mucus structural properties remains poorly understood, largely due to the lack of physiologically relevant models. To address this gap, we developed a method to collect human-cell-derived mucus that closely mimics the mechanical properties of human colonic mucus. Using this system, we investigated mucus utilization and degradation by a panel of commensal bacteria with distinct metabolic profiles. Glycan utilization by species such as Bacteroides thetaiotaomicron and Bacteroides fragilis showed no correlation with changes in mucus rheology. Instead, secreted proteases were identified as the primary driver of mucus degradation. Protease activity by B. fragilis and Bifidobacterium longum was influenced by nutrient availability, whereas in Enterococcus faecalis, it was additionally affected by oxygen exposure. E. faecalis also adapted to oxidative stress by enhancing carbohydrate metabolism and upregulating several virulence genes. Together, our findings reveal that bacterial mucus degradation is context-dependent and shaped by environmental factors. This study provides key insights into the mechanisms underlying mucus degradation and underscores the value of human cell-derived mucus models for understanding bacteria-mucus interactions in health and disease.

microbiology↗

bioRxiv2023

Coarse-grained Modeling and Experimental Investigation of the Viscoelasticity of Human Gut Mucus and Nanoparticle Dynamics

A thick layer of mucus covering the gastrointestinal tract acts as an innate barrier guarding the epithelial surface. The high molecular weight and cross-linked glycoproteins (mucins), the major building blocks of mucus, can effectively obstruct or trap invading noxious substances, such as detrimental bacteria and virus. The mucus layer as well as any trapped material can be regularly removed by the friction force from food flow and gastrointestinal peristalsis, the process of which primarily relies on the viscoelastic and shear-thinning properties. Conversely, the process by which beneficial substances, such as drug nanoparticles, cross the mucus layer and contact the epithelium is also influenced by the chemical and rheological properties of the mucus layer. Gastrointestinal disorders, most notably colitis, are often accompanied by changes to the mucosal structure. In this study, we experimentally characterized the viscoelasticity and dynamic viscosity of mucus collected from human intestinal cells. In addition, we developed a bi-component mesoscopic-scale mucus model that contained Muc2, the dominant mucin secreted in healthy individuals, and Muc5AC, which is secreted by intestinal goblet cells in certain intestinal disorders. This model enabled us to study the effects of cross-linking and mucin concentration on rheological properties of mucus. Furthermore, we quantified changes in the diffusion dynamics of nanoparticles in mucus networks caused by factors such as the size of nanoparticles, nanoparticle-mucin interactions, and the degree of mucin cross-linking.

biophysics↗

bioRxiv2020

Bacterial envelope damage inflicted by bioinspired nanospikes grown in a hydrogel

Device-associated infections are one of the deadliest complications accompanying the use of biomaterials, and despite recent advances in the development of anti-biofouling strategies, biomaterials that exhibit both functional tissue restoration and antimicrobial activity have been challenging to achieve. Here, we report the fabrication of bio-inspired bactericidal nanospikes in bacterial cellulose and investigate the mechanism underlying this phenomenon. We demonstrate these structures affects preferentially stiff membranes like those in Gram-positive bacteria, but exhibit cytocompatibility towards mammalian cells, a requisite for tissue restoration. We also reveal the bactericidal activity of the nanospikes is due to a pressure-induced mechanism, which depends on the cells adherence time, nanospikes geometry and spacing, cell shape, and mechanical properties of the cell wall. Our findings provide a better understanding of the mechanobiology of bacterial cells at the interface with nanoscale structures, which is fundamental for the rational design bactericidal topographies.

bioengineering↗

bioRxiv2020

E. coli adhesion and biofilm formation on polydimethylsiloxane are independent of substrate stiffness

Bacterial adhesion and biofilm formation on the surface of biomedical devices is a detrimental process that compromises patient safety and material functionality. Several physicochemical factors are involved in biofilm growth, including the surface properties. Among those, material stiffness has recently been suggested to influence microbial adhesion and biofilm growth in a variety of polymers and hydrogels. However, no clear consensus exists about the role of material stiffness on biofilm initiation and whether very compliant substrates are deleterious to bacterial cell adhesion. Here, by systematically tuning substrate topography and stiffness while keeping the surface free energy of polydimethylsiloxane substrates constant, we show that topographical patterns at the micron and submicron scale impart unique properties to the surface that are independent of the material stiffness. The current work provides a better understanding of the role of material stiffness on bacterial physiology and may constitute a cost-effective and simple strategy to reduce bacterial attachment and biofilm growth even in very compliant and hydrophobic polymers.

bioengineering↗