Geometric constraint-triggered collagen expression mediates bacterial-host adhesion.

Area of Science:

• Biophysics
• Cell Biology
• Microbiology

Background:

• Geometrically confined microenvironments are common in physiological processes like wound healing.
• The influence of spatial constraints on host cell-bacteria interactions remains largely unknown.

Purpose of the Study:

• To investigate how spatial geometric constraints on host cells regulate bacteria-host interactions.
• To elucidate the mechanisms underlying location-dependent bacterial adhesion in confined cell monolayers.
• To explore potential therapeutic strategies targeting these interactions.

Main Methods:

• Studied bacteria-host cell interactions in spatially constrained cell monolayers.
• Measured bacterial adhesion forces using atomic force microscopy.
• Performed single-cell RNA sequencing to analyze gene expression.
• Utilized collagen IV inhibitors and conducted animal experiments.

Main Results:

• Bacteria exhibited spatial heterogeneity in adhesion, preferentially binding to cells at the edges of confined monolayers.
• Bacterial adhesion forces were significantly higher at monolayer edges (up to 75 nN) compared to centers, influenced by substrate rigidity.
• Spatially heterogeneous collagen IV expression, particularly edge effects, was identified as the cause of location-dependent bacterial adhesion.

Conclusions:

• Spatial geometry critically influences bacteria-host cell interactions, leading to preferential adhesion at monolayer edges.
• Collagen IV expression patterns mediate this edge effect and dictate bacterial adhesion.
• Collagen IV inhibitors show promise as adjuvants to enhance antibiotic efficacy by reducing bacterial adhesion.