Atomic Force Microscopy in Cell Mechanics and Biological Systems

Atomic force microscopy (AFM) has emerged as an indispensable technique for probing the mechanical and structural properties of living cells at nanometre resolution. By employing a sharp probe to indent or scan the cell surface, AFM quantifies topography, stiffness and adhesion forces under physiological conditions. These measurements reveal the viscoelastic behaviour of the plasma membrane, cytoskeleton and subcellular compartments, offering insights into mechanotransduction, cell migration, division and tissue development. AFM studies have elucidated how alterations in cellular stiffness correlate with disease phenotypes such as cancer metastasis, neurodegeneration and cardiovascular dysfunction. The capacity to integrate AFM with optical microscopy, microfluidic devices and novel cantilever designs has expanded its utility for real‐time observation of dynamic processes, multiplexed assays of cell–cell interactions and mechanochemical mapping. As a result, AFM stands at the forefront of mechanobiology, underpinning efforts to develop biomechanical biomarkers, guide drug discovery and engineer tissue scaffolds that mimic native mechanical microenvironments.

Research from Nature Portfolio

Recent work has employed AFM to quantify erythrocyte–erythrocyte adhesion in the presence of fibrinogen, demonstrating that plasma protein binding increases detachment forces and alters cell morphology. A mathematical model calibrated with AFM data captures the energetics of intercellular adhesion and predicts how aggregation impedes microcirculatory flow in cardiovascular disease.

Another study integrates quantitative imaging AFM with laser scanning confocal microscopy to achieve simultaneous mapping of cell surface mechanics and fluorescently tagged biomolecules. This correlative approach reveals how exposure to environmental stressors alters membrane adhesion, cytoskeletal organisation and oxidative stress responses in bacterial, fungal and human cells in real time.

Atomic Force Microscopy in Cell Mechanics and Biological Systems publication trend

The graph below shows the total number of articles in atomic force microscopy in cell mechanics and biological systems across all publications each year (not limited to Nature Index journals).

Technical terms

Atomic Force Microscopy (AFM): A technique that uses a nanometre-sharp probe to map surface topography and mechanical properties by measuring probe–sample interactions.

Nanoindentation: A method of pressing a sharp tip into a material to determine its hardness and elastic modulus from force–displacement curves.

Young’s Modulus: A measure of a material’s stiffness defined as the ratio of stress to strain in the elastic deformation regime.

Viscoelasticity: The property of materials that exhibit both viscous and elastic responses when subjected to deformation.

Correlative AFM-LSCM: An integrated approach combining atomic force microscopy with laser scanning confocal microscopy for concurrent mechanical and fluorescence imaging.

References

1. A mathematical model of fibrinogen-mediated erythrocyte–erythrocyte adhesion. Communications Biology (2023).
2. Correlative atomic force microscopy quantitative imaging-laser scanning confocal microscopy quantifies the impact of stressors on live cells in real-time. Scientific Reports (2018).
3. Single‐Cell Elastography: Probing for Disease with the Atomic Force Microscope. Disease Markers (2004).
4. Stiffness tomography of eukaryotic intracellular compartments by atomic force microscopy. Nanoscale (2019).
5. AFM and Fluorescence Microscopy of Single Cells with Simultaneous Mechanical Stimulation via Electrically Stretchable Substrates. Materials (2021).