Force activates cell-cell aggregation of yeast by activating amyloid-like protein aggregation

What is it about?

In yeast cell adhesion proteins, extension force (pulling on the molecules) exposes amyloid-forming sequences, that cluster the cell adhesin proteins on the cell surface, and greatly increase the strength and duration of yeast-to-yeast binding. We show here that the Saccharomyces cerevisiae (bakers' and brewers' yeasts) cell adhesion proteins called flocculins follow this model. Force induces surface clustering of the flocculins, then leads to increased cell-to cell binding and simultaneously increased binding of amyloid-binding dyes. Anti-amyloid treatments prevent this activation, disrupt flocs of cells, and inhibit the ability of the focculins to help the yeast cells invade agar. Although the flocculins are normally activated by Ca++ ion, shear force can partially activate the flocculins, even in the absence of Ca++. Thus shear force and added Ca++ can both activate amyloid-like interactions of the flocculins, and lead to increased cellular aggregation.

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Why is it important?

The Saccharomyces cerevisiae flocculins mediate the formation of cellular aggregates and biofilm-like mats, useful in clearing yeast from fermentations. An important property of fungal adhesion proteins, including flocculins, is the ability to form catch bonds, i.e., bonds that strengthen under tension. This paper demonstrates that amyloid-like interactions greatly increase the flocculation ability, and thus extends a new model for force-responsive functional amyloids to adhesion proteins from two new gene families, and to baker's and brewer's yeast. The results demonstrate the applicability of the Als adhesin model and provide a rational framework for the enhancement or inhibition of flocculation in industrial applications.