Abstract
BackgroundThe initial step of a number of human or plant fungal infections requires active penetration of host tissue. For example, active penetration of intestinal epithelia by Candida albicans is critical for dissemination from the gut into the bloodstream. However, little is known about how this fungal pathogen copes with resistive forces upon host cell invasion.ResultsIn the present study, we have used PDMS micro-fabrication to probe the ability of filamentous C. albicans cells to penetrate and grow invasively in substrates of different stiffness. We show that there is a threshold for penetration that corresponds to a stiffness of ~ 200 kPa and that invasive growth within a stiff substrate is characterized by dramatic filament buckling, along with a stiffness-dependent decrease in extension rate. We observed a striking alteration in cell morphology, i.e., reduced cell compartment length and increased diameter during invasive growth, that is not due to depolarization of active Cdc42, but rather occurs at a substantial distance from the site of growth as a result of mechanical compression.ConclusionsOur data reveal that in response to this compression, active Cdc42 levels are increased at the apex, whereas active Rho1 becomes depolarized, similar to that observed in membrane protrusions. Our results show that cell growth and morphology are altered during invasive growth, suggesting stiffness dictates the host cells that C. albicans can penetrate.
Highlights
The initial step of a number of human or plant fungal infections requires active penetration of host tissue
We show that there is a threshold for penetration that corresponds to a stiffness of ~ 200 kPa and that invasive growth within a stiff substrate is characterized by dramatic filament buckling along with a stiffness-dependent decrease in extension rate
C. albicans cells were mixed with fetal calf serum, added to the PDMS array, incubated for ~ 1 h, and subsequently, filamentous growth was followed over time (Fig. 1d)
Summary
The initial step of a number of human or plant fungal infections requires active penetration of host tissue. Fungal pathogens have turgor pressures in the MPa range [3, 4], and for human fungal pathogens, this turgor pressure exceeds host cell resistance to penetration Such host cells have elastic moduli that are in the 1–100 kPa range [5,6,7], the critical stress for material rupture is determinant. Both the human fungal pathogens Candida albicans [8] and Aspergillus fumigatus [9] can actively penetrate host tissue, which is a critical step in the infection process [10,11,12,13,14]. Previous studies have shown that C. albicans hyphal tips are asymmetrically positioned during growth on a stiff surface, i.e., a “nose down” morphology, and that perpendicular growth and contact to a stiff topographical ridge (less than the hyphal radius) results in an indentation of the ridge [19]
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