Common yeast Candida albicans as a wild-type cell presents an ovoid shape; in its pathogenic morphology, C. albicans develops a germ tube which develops into a hypha. Development of a hypha is theorized to act as a mechanism for cell survival in less-than optimal environments, such as within the human body. In addition to human serum inducing hyphal growth, C. albicans' development of hyphae occurs when the cells are under stress, in basic pH, or exposed to a variety of amino acids. While the environments in which hyphae form are well known, the biomechanical changes associated with this transition are less investigated. Our technique combines the use of an atomic force microscope in contact mode with its force-distance spectroscopy capability to determine the cell stiffness of C. albicans in its various morphological states. By measuring cell stiffness in both the cytosol and nucleus for wild-type form and pseudohyphal morphology, and in cytosol and hypha for the hyphal morphology, we are able to determine the degree by which the cell loses its pliability as it assumes pathogenicity. Because of these implications of hyphal growth, we expect the stiffness of C. albicans to be significantly higher than that of its pseudohyphal morphology or wild-type form.

In non-covalent biological adhesion, molecular bonds commonly exhibit a monotonously decreasing life time when subjected to tensile forces (slip bonds). In contrast, catch bonds behave counter intuitively, as they show an increased life time within a certain force interval. To date only a hand full of catch bond displaying systems have been identified. In order to unveil their nature, a number of structural and phenomenological models have been introduced. Regardless of the individual causes for catch bond behavior, it appears evident that the free energy landscapes of these interactions bear more than one binding state. Here, we investigated the catch bond interaction between the hydrophilic domain of the human cell surface sulfatase 1 (Sulf1HD) and its physiological substrate heparan sulfate (HS) by atomic force microscopy based single molecule force spectroscopy (AFM-SMFS). Using Jarzynski’s equality, we estimated the associated Gibbs free energy and provide a comprehensive thermodynamic and kinetic characterization of Sulf1HD/HS interaction. Interestingly, the binding potential landscape exhibits two distinct potential wells which confirms the recently suggested two state binding. Even though structural data of Sulf1HD is lacking, our results allow to draft a detailed picture of the directed and processive desulfation of HS.