Gigantol Preserves Lens Biophysical Homeostasis by Restoring Cytoskeletal Integrity and Membrane Fluidity in a Diabetic Cataract Model

Diabetic cataract (DC) is a major complication of diabetes, with human lens epithelial cells (HLECs) playing a central role in its pathogenesis. Gigantol, a natural compound, has demonstrated protective effects against HLEC damage, yet its underlying mechanisms, particularly concerning cellular biophysical properties, remain poorly understood. This study investigated the protective role of gigantol against high-glucose-induced damage in HLECs, with a specific focus on alterations in cellular biophysical properties. Using a multi-technique approach including transmission electron microscopy (TEM), atomic force microscopy, laser scanning confocal microscopy, and Raman spectroscopy, we analyzed changes in ultrastructure, morphology, stiffness, roughness, membrane fluidity, and cytoskeletal organization. Treatment with gigantol effectively restored cellular ultrastructure, mitigated cytoskeletal disruption, and normalized key biomechanical properties: it reduced cell stiffness and roughness by approximately one-fourth, increased cell height by nearly onefold, and enhanced membrane fluidity by one-fifth. Raman spectroscopy indicated that gigantol improved membrane fluidity by modulating lipid bilayer structure, specifically through alterations in -CH₂- bending and -C=C- stretching modes. These findings demonstrate that gigantol protects HLECs from high-glucose-induced damage not only by biochemical means but also by restoring cellular biophysical homeostasis. This study provides novel biophysical-pathological insights into the anti-cataract mechanism of gigantol, highlighting its potential as a therapeutic agent that targets both biochemical and biophysical aspects of DC.