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Research into materials for medical application draws inspiration from naturally occurring or synthesized surfaces, just like many other research directions. For medical application of materials, particular attention has to be paid to biocompatibility, osseointegration, and bacterial adhesion behavior. To understand their properties and behavior, experimental studies with natural materials such as teeth are strongly required. The results, however, may be highly case-dependent because natural surfaces have the disadvantage of being subject to wide variations, for instance in their chemical composition, structure, morphology, roughness, and porosity. A synthetic surface which mimics enamel in its performance with respect to bacterial adhesion and biocompatibility would, therefore, facilitate systematic studies much better. In this study, we discuss the possibility of using hydroxyapatite (HAp) pellets to simulate the surfaces of teeth and show the possibility and limitations of using a model surface. We performed single-cell force spectroscopy with single

Caries is one of the most prevalent diseases worldwide, which is caused by the degradation of the tooth enamel surface. In earlier research the opportunistic pathogen Candida albicans has been associated with the formation of caries in children. Colonization of teeth by C. albicans starts with the initial adhesion of individual yeast cells to the tooth enamel surface. In this study, we visualized the initial colonization of C. albicans yeast cells on pellicle-covered enamel by scanning electron microscopy. To quantitatively unravel the initial adhesion strength, we applied fluidic force microscopy-based single-cell force spectroscopy to examine the key adhesion parameters adhesion force, rupture length and de-adhesion work. We analyzed single saliva-treated or untreated yeast cells on tooth enamel specimens with or without salivary pellicle. Under all tested conditions, adhesion forces in the lower nanonewton range were determined. Furthermore, we have found that all adhesion parameters were enhanced on the pellicle-covered compared to the uncovered enamel. Our data suggest that initial adhesion occurs through a strong interaction between yeast cell wall-associated adhesins and the salivary pellicle. Future SCFS studies may show whether specific management of the salivary pellicle reduces the adhesion of C. albicans on teeth and thus contributes to caries prophylaxis.

Candida albicans-related bloodstream infections are often associated with infected central venous catheters (CVC) triggered by microbial adhesion and biofilm formation. We utilized single-cell force spectroscopy (SCFS) and flow chamber models to investigate the adhesion behavior of C. albicans yeast cells and germinated cells to naïve and human blood plasma (HBP)-coated CVC tubing. Germinated cells demonstrated up to 56.8-fold increased adhesion forces to CVC surfaces when compared to yeast cells. Coating of CVCs with HBP significantly increased the adhesion of 60-min germinated cells but not of yeast cells and 30-min germinated cells. Under flow conditions comparable to those in major human veins, germinated cells displayed a flow directional-orientated adhesion pattern to HBP-coated CVC material, suggesting the germ tip to serve as the major adhesive region. None of the above-reported phenotypes were observed with germinated cells of an als3Δ deletion mutant, which displayed similar adhesion forces to CVC surfaces as the isogenic yeast cells. Germinated cells of the als3Δ mutant also lacked a clear flow directional-orientated adhesion pattern on HBP-coated CVC material, indicating a central role for Als3 in the adhesion of germinated C. albicans cells to blood exposed CVC surfaces. In the common model of C. albicans, biofilm formation is thought to be mediated primarily by yeast cells, followed by surface-triggered the formation of hyphae. We suggest an extension of this model in which C. albicans germ tubes promote the initial adhesion to blood-exposed implanted medical devices via the germ tube-associated adhesion protein Als3.

Staphylococcus aureus is a common cause of catheter-related blood stream infections (CRBSI). The bacterium has the ability to form multilayered biofilms on implanted material, which usually requires the removal of the implanted medical device. A first major step of this biofilm formation is the initial adhesion of the bacterium to the artificial surface. Here, we used single-cell force spectroscopy (SCFS) to study the initial adhesion of S. aureus to central venous catheters (CVCs). SCFS performed with S. aureus on the surfaces of naïve CVCs produced comparable maximum adhesion forces on three types of CVCs in the low nN range (~ 2-7 nN). These values were drastically reduced, when CVC surfaces were preincubated with human blood plasma or human serum albumin, and similar reductions were observed when S. aureus cells were probed with freshly explanted CVCs withdrawn from patients without CRBSI. These findings indicate that the initial adhesion capacity of S. aureus to CVC tubing is markedly reduced, once the CVC is inserted into the vein, and that the risk of contamination of the CVC tubing by S. aureus during the insertion process might be reduced by a preconditioning of the CVC surface with blood plasma or serum albumin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.