Extracellular matrix chemistry tunes bacterial biofilm metabolism and optimizes fitness

Abstract

Chemically complex extracellular matrices define cellular microenvironments and shape cell behavior across all domains of life. But how has evolution optimized these materials to ensure the success of multicellular communities? Inspired by the well-established composition–properties–function relationships in engineered materials, we hypothesized that analogous relationships exist in extracellular matrices, where the composition and interactions among various matrix components govern material properties and cellular physiology. Here, we examine Pseudomonas aeruginosa biofilms—representative of ubiquitous multicellular microbial assemblies in nature and disease. We show that electrostatic interactions between the cationic polysaccharide Pel and extracellular DNA (eDNA) compete with eDNA binding to pyocyanin (PYO), a diffusible redox-active metabolite that supports anaerobic metabolism via extracellular electron transfer (EET). From a materials perspective, biofilm-mimetic hydrogels and natural biofilms revealed that altering Pel’s charge via pH adjustment or chemical acetylation, or tuning the Pel:eDNA ratio, directly and predictably modulates PYO retention and EET efficiency. Biologically, a lower Pel:eDNA ratio enhances biofilm metabolism under oxygen limitation, whereas a higher ratio promotes survival under antibiotic stress. Notably, these perturbations (pH, Pel structure, and abundance) can be achieved directly or indirectly through biological activities. Together, these findings highlight how biologically regulated matrix chemistry encodes tunable material properties that, in turn, affect cellular responses that confer biofilm fitness advantages. They further suggest cells might actively fine-tune the surrounding matrix chemistry to maximize survival across diverse environments. More broadly, our work establishes a materials-based framework for a mechanistic understanding of the biological functions of extracellular matrix components in multicellular communities.