Perspective: The viscoelastic properties of biofilm infections and mechanical interactions with phagocytic immune cells

Abstract

Biofilms are viscoelastic materials that are a prominent public health problem and a cause of most chronic bacterial infections, in large part due to their resistance to clearance by the immune system. Viscoelastic materials combine both solid-like and fluid-like mechanics, and the viscoelastic properties of biofilms are an emergent property of the intercellular cohesion characterizing the biofilm state (planktonic bacteria do not have an equivalent property). However, how the mechanical properties of biofilms are related to the recalcitrant disease that they cause, specifically to their resistance to phagocytic clearance by the immune system, remains almost entirely unstudied. We believe this is an important gap that is ripe for a large range of investigations. Here we present an overview of what is known about biofilm infections and their interactions with the immune system, biofilm mechanics and their potential relationship with phagocytosis, and we give an illustrative example of one important biofilm-pathogen (Pseudomonas aeruginosa) which is the most-studied in this context. We hope to inspire investment and growth in this relatively-untapped field of research, which has the potential to reveal mechanical properties of biofilms as targets for therapeutics meant to enhance the efficacy of the immune system.

Keywords: biofilm; immune system; neutrophil; phagocytosis; rheology; viscoelasticity.

Figure 1

Bulk rheology and micro-rheology approaches for measuring biofilm mechanics. Typical bulk rheology grows a sample ex situ, which is then loaded into a holder and has a particular deformation applied. To measure shear moduli, the sample is typically placed in parallel plates ~ 1mm apart on a rotational rheometer. The plates apply a controlled stress or strain shear deformation, taking into account plate diameter and gap. For extension or compression measurements, typically a dynamic mechanical analyzer is used that has a range of sample holders which similar dimensions. In multi-particle tracking microrheology samples are grown in situ with particles within a sample holder. This system is then directly placed onto a microscope and particle motion is tracked. Typical particle sizes are ~ 1 micron. Created with BioRender.com.

Figure 2

Possible route toward increasing biofilm susceptibility to phagocytic clearance by compromising matrix mechanics. Polysaccharide-degrading enzymes such as α-amylase (targeting α-1,4-glycosidic linkages) and cellulase (targeting β-1,4-glycosidic linkages), as well as nucleic acid-targeting enzymes such as DNase, could be utilized to disrupt the biofilm matrix and disperse bacterial cells. Release from the protective biofilm EPS could increase susceptibility to immune clearance through routes including neutrophil phagocytosis. Created with BioRender.com.