Nanobiomechanics in Oncology: Atomic Force Microscopy for Cancer Mechanophenotyping Using Cellular Young's Modulus

This review examines the current literature on the application of atomic force microscopy (AFM) to cancer mechanophenotyping, with particular emphasis on cellular Young's modulus and its potential diagnostic significance. A structured electronic search of PubMed, Scopus and Google Scholar was conducted to identify studies published between 1999 and 2025 reporting AFM-based measurements of cellular Young's modulus in cancer-related models. Across multiple malignancies, reduced cellular stiffness is frequently observed in malignant compared with non-malignant cells and is associated with cytoskeletal remodelling, increased deformability and altered cell-matrix interactions. However, the relationship between Young's modulus and malignancy is not universally monotonic. Nanomechanical properties may vary across different pathological states and malignant phenotypes rather than following a simple monotonic trajectory, while invasive and metastatic cells can dynamically remodel their cytoskeleton and modify their stiffness in response to environmental and mechanical constraints. Young's modulus should therefore not be regarded as an isolated universal cancer biomarker, but rather as one component of a dynamic mechanophenotype influenced by disease stage, cellular region, microenvironment and measurement methodology. Recent advances in automated force acquisition, optical cell recognition, artificial intelligence and high-throughput AFM are beginning to address traditional limitations in measurement efficiency and operator dependence. The future diagnostic value of AFM may therefore lie in integrating Young's modulus with complementary parameters, including spatial mechanical heterogeneity, viscoelasticity, adhesion, deformation-energy characteristics and nanotopography, to define multidimensional cancer mechanophenotypes. Standardised acquisition and analysis protocols, together with validation in patient-derived specimens, will be essential for translating AFM nanomechanics from an experimental measurement into a clinically informative biomechanical biomarker.