Decoding the pathogenesis of Candida albicans infection and evaluating the efficacy of antifungal drugs using atomic force microscopy.

Atomic force microscopy (AFM) has emerged as a pivotal method enabling multidimensional characterization of Candida albicans (C. albicans) by simultaneously providing topographical imaging, mechanical profiling, and quantitative measurements of adhesion forces under near-physiological conditions. AFM-derived data demonstrate that nanoscale surface alterations, including wrinkling, indentations, increased roughness, and perforations correlate closely with modulation of the Young's modulus and with the reorganization of mannoproteins and adhesins, particularly those of the Als family. The co-occurrence of structural, mechanical, and adhesive changes reflects the dynamic remodeling of the fungal cell wall that governs morphogenesis, virulence, and biofilm formation. AFM offers high resolution insight into the mechanisms of action of antifungal drugs, antimicrobial peptides, nanomaterials, and physical treatments that destabilize the cell wall, reduce its stiffness, or conversely induce compensatory stiffening and adhesin exposure. As a result, the technique enables the identification of critical steps in stress responses and hyperadhesive phenotypes that contribute to fungal invasion and treatment resistance. Integration of AFM with spectroscopic and microfluidic approaches further enhances its potential to reveal new therapeutic targets. Collectively, evidence from numerous studies underscores AFM as a foundational tool in the rational design of modern, multimodal antifungal strategies aimed at the cell wall and biofilm of C. albicans.