Spotlight on membrane fluidity of normal and cancer cells: Implications for cancer diagnosis and treatment

Abstract

Membrane fluidity is crucial for cellular function, signalling, and adaptation. Healthy cells maintain strict control over membrane fluidity through homeostatic mechanisms such as lipid-protein interactions, phospholipid asymmetry and cholesterol distribution. In contrast, cancer cells exhibit profound dysregulation. Altered lipid metabolism, increased incorporation of unsaturated fatty acids and disrupted cholesterol homeostasis create a more fluid and dynamic membrane environment, thereby enhancing oncogenic signalling, mechanotransduction and immune evasion. These changes are key drivers of cancer behaviours, including enhanced proliferation, resistance to apoptosis and metastasis.

This review explores the biophysical basis of membrane fluidity, examining its dual role as a diagnostic biomarker and a therapeutic target in cancer. Advanced imaging techniques, such as fluorescence recovery after photobleaching (FRAP), fluorescence lifetime imaging microscopy (FLIM) and electron spin resonance (ESR), enable precise measurement of membrane fluidity, revealing cancer-specific alterations. These tools provide high-resolution insights into lipid organization and protein mobility, facilitating improved cancer diagnostics and therapeutic response monitoring. Emerging therapeutic strategies exploit membrane fluidity to selectively induce cancer cell death. These strategies include modulating cholesterol levels, using lipid metabolism inhibitors, and activating sonosensitisers, intracellular responsive chemical agents that generate reactive oxygen species, using ultrasound by sonodynamic therapy.

Despite these advances, there are still challenges in translating membrane-targeted strategies into clinical practice, primarily due to tumour heterogeneity and the complex relationship between lipid dynamics and protein function. Future research must integrate lipidomics, biophysics, and oncology to exploit membrane fluidity as a biomarker and therapeutic target, paving the way for more precise cancer treatments.