Molecular Forces in Biofilms

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Central to the initiation and maturation of biofilms are the bacterial cell surface adhesion molecules (adhesins) that mediate initial attachment between the cell and a wide range of surfaces. Atomic force microscopy (AFM)-based single-molecule and single-cell force spectroscopy will be used to quantify the binding forces of bacterial adhesins responsible for initial attachment. A central question to be addressed is what determines this nanoscale interplay between the properties of the underlying substrate and bacterial adhesins.

Bacterial Rigidity Sensing

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Rigidity sensing or how adherent cells respond to the stiffness of the underlying substrate is well-known in mammalian cells and is established to influence important biological processes such as stem cell differentiation and cancer cell metastasis. Discovery of rigidity sensing in bacteria however is still rather recent. By quantifying the mechanical forces that govern the interaction of key adhesins with substrates of varying stiffness, we aim to paint a more unified molecular picture of bacterial rigidity sensing.

Structure and Nanomechanics of Bacterial Biofilms

To understand how the properties of the underlying substrate influence the structure and nanomechanics of biofilms, Quantitative Imaging, which allows for a simultaneous acquisition of the biofilm topography and its nanomechanical properties (local stiffness, deformation, adhesive properties), will be carried out in biofilms grown on substrates with different properties. With this method, high-resolution images of EPS (extracellular polymeric substance) as well as heterogeneities on the cell surface can also be achieved. This underscores the importance of nanoscale studies on biofilms. In addition, correlated optical and AFM imaging will be used to differentiate the location of EPS and cells on substrates. This will serve as an optical guide for force measurements.

Targeted delivery of anti-biofilm agents

 

In this project, we aim to develop a multifunctional and stimuli-responsive nanovehicles―for a spatially- and temporally-controlled delivery of formulations specific to biofilms. These nanocarriers will be loaded with antimicrobial agents, quorum sensing inhibitors, and EPS-degrading molecules―that will target, in a defined manner, the different major contributors of biofilms. This is in line with one of our primary goals—development of novel anti-adhesion therapy.