Mechanical force-induced morphology changes in a human fungal pathogen

Area of Science:

• Mycology
• Biophysics
• Cell Biology

Background:

• Fungal infections often require active host tissue penetration.
• Candida albicans invasion of intestinal epithelia is key for bloodstream dissemination.
• Mechanisms of fungal pathogen adaptation to host tissue resistance are poorly understood.

Purpose of the Study:

• To investigate how filamentous Candida albicans penetrates and grows in substrates of varying stiffness.
• To understand the cellular and mechanical responses of C. albicans during invasive growth.

Main Methods:

• Utilized PDMS (polydimethylsiloxane) micro-fabrication to create substrates with controlled stiffness.
• Examined the invasive growth and cellular morphology of C. albicans on these substrates.
• Analyzed the localization and activity of key proteins like Cdc42 and Rho1.

Main Results:

• Identified a penetration threshold stiffness of approximately 200 kPa for C. albicans.
• Observed filament buckling and reduced extension rates in stiffer substrates.
• Documented altered cell morphology (shorter compartments, wider diameter) due to mechanical compression, not Cdc42 depolarization.

Conclusions:

• Mechanical compression during invasive growth alters C. albicans cell morphology and growth.
• Increased Cdc42 activity at the apex and Rho1 depolarization occur in response to compression.
• Substrate stiffness is a critical factor determining the host cells that C. albicans can penetrate.