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Authors
Supervisors
Dufrêne, Yves
Abstract
(en) Unraveling the structure-function relationships of the yeast cell wall is a major challenge in current microbiology and offers exciting prospects in biomedicine. A key question is to understand how cell wall proteins respond to mechanical force and how this response could be related to function. The aim of this thesis is to gain insight in the nanoscale surface properties of the cell wall of Saccharomyces cerevisiae and Candida albicans, with an emphasis on the nanomechanics of the membrane sensor Wsc1 and of the cell adhesion protein Als5p. The methodology involved developing atomic force microscopy (AFM) techniques for live cell analysis, in combination with genetics and cell biology tools. We first investigated the nanomechanics of Wsc1 sensors, revealing that they behave like nanosprings capable to resist mechanical force and to respond to stressing conditions. The data provide direct evidence that Wsc1 functions as a mechanosensor capable of feeling mechanical force, and, in turn, activating intracellular signaling cascades. We next explored the elasticity of Als5p adhesins. Stretching single adhesins yielded sawtooth force patterns corresponding to the force-induced unfolding of individual tandem repeats. The unfolding probability increased with the number of tandem repeats and correlated with the level of cell adherence. The results suggest that the modular and flexible nature of Als5p conveys both strength and toughness to the protein, making it ideally suited for cell adhesion. Furthermore, we showed that the precise delivery of piconewton forces on the yeast surface triggers the formation and propagation of adhesion nanodomains, that we call “nanoadhesomes”. Such force-dependent adhesion domains may be a general mechanism for activating cell adhesion. This work offers new opportunities to fight pathogens using anti-adhesion drugs.
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Alsteens, D. (2011). Nanomechanics of the yeast cell wall. https://hdl.handle.net/2078.5/49925