Mechanical force-induced morphology changes in a human fungal pathogen
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RESEARCH ARTICLE
Open Access
Mechanical force-induced morphology changes in a human fungal pathogen Charles Puerner1†, Nino Kukhaleishvili1,2†, Darren Thomson1,3†, Sebastien Schaub1,4, Xavier Noblin2*, Agnese Seminara2, Martine Bassilana1 and Robert A. Arkowitz1*
Abstract Background: The 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. Results: In 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. Conclusions: Our 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. Keywords: Cell invasion, Mechanical force, Cell polarity, Cdc42, Cell morphology
Background Polar tip growth, in which extension is limited to the apical surface, enables walled cells such as fungi and plants to explore their environment for nutrients and mating partners, while maintaining their surface to volume ratio [1]. Campas and Mahadevan [2] have derived simple scaling laws for cell geometry and identified a single dimensionless parameter that is * Correspondence: [email protected]; [email protected] † Charles Puerner, Nino Kukhaleishvili, and Darren Thomson are co-first authors; order was determined by contribution to figures. 2 Université Côte d’Azur, CNRS, Institute Physics of Nice (INPHYNI), Ave. J. Vallot, Nice, France 1 Université Côte d’Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), Parc Valrose, Nice, France Full list of author information is available at the end of the article
sufficient to describe variation in the shape of tip growing cells using turgor pressure, cell wall elastic properties, and secretion rate. However, little is known with respect to the response of tip growing cells to mechanical stress. There are five fundamental types of mechanical stress: tension, compression, shear, torsion, and bending. Human and plant fungal pathogens can penetrate h
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