Single-cell mechanodynamics: Probing cellular function through nanomotion and intracellular mechanics

Living cells continuously consume energy to sustain their structure, mechanics, and function. Energy-dependent nanometer-scale mechanical fluctuations, called nanomotion, provide a label-free physical readout of this activity in individual cells. When interpreted as dynamic signatures of cellular activity, these fluctuations form the basis of single-cell mechanodynamics. In this review, we examine how such fluctuations can be measured and interpreted across biomolecular, organellar, and cellular scales. We discuss established mechanodynamic sensing modalities, including atomic force microscope (AFM) cantilever sensing and optical nanomotion detection (ONMD), together with complementary approaches and AFM nanoendoscopy, which provides direct access to intracellular mechanical properties and establishes an experimental foundation for future organelle-level mechanodynamic measurements. We consider how mechanodynamic readouts are being applied in antimicrobial susceptibility testing (AST), mechanobiology, functional phenotyping, disease physiology, and life detection. Collectively, these developments support single-cell mechanodynamics as an emerging framework for linking structure, mechanics, metabolism, perturbation responses, and cellular function.