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Host Cell Geometry and Cytoskeletal Organization Governs Candida-Host Cell Interactions at the Nanoscale
Easter Ndlovu1, Lucas Malpartida2, Taranum Sultana1
1Department of Chemistry and Biochemistry, University of Regina, 3737 Wascana Parkway, Regina S4S 0A2, Saskatchewan, Canada.
Abstract:
Candida is one of the most common opportunistic fungal pathogens in humans. Its adhesion to the host cell is required in parasitic states and is important for pathogenesis. Many studies have shown that there is an increased risk of developing candidiasis when normal tissue barriers are weakened or when immune defenses are compromised, for example, during cancer treatment that induces immunosuppression. The mechanical properties of malignant cells, such as adhesiveness and viscoelasticity, which contribute to cellular invasion and migration are different from those of noncancerous cells. To understand host invasion and its relationship with host cell health, we probed the interaction of Candida spp. with cancerous and noncancerous human cell lines using atomic force microscopy in the single-cell force spectroscopy mode. There was significant adhesion between Candida and human cells, with more adhesion to cancerous versus noncancerous cell lines. This increase in adhesion is related to the mechanobiological properties of cancer cells, which have a disorganized cytoskeleton and lower rigidity. Altered geometry and cytoskeletal disruption of the human cells impacted adhesion parameters, underscoring the role of cytoskeletal organization in Candida-human cell adhesion and implicating the manipulation of cell properties as a potential future therapeutic strategy.
Insights
Candida fungi adhere more strongly to cancer cells than healthy cells. This increased adhesion is linked to cancer cells
Area of Science:
- Mycology
- Cell Biology
- Biophysics
Background:
- * *Candida* species are opportunistic fungal pathogens causing candidiasis, particularly in immunocompromised individuals.
- * Host cell adhesion is crucial for *Candida* pathogenesis and parasitic survival.
- * Cancer cells exhibit distinct mechanical properties (adhesiveness, viscoelasticity) influencing invasion and migration.
Purpose of the Study:
- * To investigate the adhesion mechanisms between *Candida* and both cancerous and noncancerous human cell lines.
- * To correlate host cell mechanobiological properties with the degree of *Candida* adhesion.
- * To explore the role of cytoskeletal organization in host-pathogen interactions.
Main Methods:
- * Atomic Force Microscopy (AFM) in single-cell force spectroscopy mode.
- * Probing the interaction forces between *Candida* species and human cell lines (cancerous vs. noncancerous).
Main Results:
- * Significant adhesion observed between *Candida* and human cells.
- * Greater adhesion occurred between *Candida* and cancerous cell lines compared to noncancerous ones.
- * Increased adhesion correlated with cancer cells' disorganized cytoskeleton and reduced rigidity.
Conclusions:
- * *Candida* adhesion is significantly influenced by the mechanobiological properties of host cells.
- * Cancer cells' altered mechanical properties, including cytoskeletal disorganization, promote enhanced fungal adhesion.
- * Manipulating host cell mechanical properties presents a potential therapeutic avenue for candidiasis.
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The cytoskeleton is a network of protein filaments present within the cell, having three distinct filaments ̶ microfilaments, microtubules, and intermediate filaments. Each has characteristic features that distinguish them, including the dynamics of their assembly and disassembly, mechanical properties, polarity, and the type of molecular motors associated with them. Earlier, they were thought to be present only in eukaryotic cells; however, their...

