Mechanobiology of Immune Cell Function

In recent years, the mechanobiology of immune cells has emerged as a critical field that examines how physical forces and the mechanical properties of the microenvironment influence fundamental immune functions. Immune cells such as macrophages and dendritic cells traverse tissues with varying stiffness, topographies and mechanical stress, which shape their migration, activation, phenotypic polarisation and cytokine secretion. Mechanotransduction pathways couple extracellular signals from the matrix or cell–cell contacts to intracellular cytoskeletal rearrangements and gene regulation. This interplay with biochemical cues underpins tissue repair, inflammation resolution and the immune response to infection and tumours. A deeper understanding of these processes offers new insights for immunomodulatory therapies, the design of biomaterial scaffolds in regenerative medicine and precision approaches in immuno-oncology.

Research from Nature Portfolio

Studies have demonstrated that substrate stiffness profoundly influences dendritic cell function. When human dendritic cells were cultured on polyacrylamide substrates of low (2 kPa), intermediate (12 kPa) and high (50 kPa) stiffness, immature cells exhibited stiffness-dependent regulation of C-type lectin expression, affecting antigen uptake. Increased rigidity also altered β2 integrin levels and podosome formation, while in mature cells it upregulated CD83 and CCR7, enhancing chemokine-directed migration. These findings reveal that mechanical cues within tissues fine-tune antigen presentation and migratory capacity, with implications for adaptive immune priming and vaccine strategies.

Mechanobiology of Immune Cell Function publication trend

The graph below shows the total number of articles in mechanobiology of immune cell function across all publications each year (not limited to Nature Index journals).

Technical terms

Mechanotransduction: Process by which cells convert mechanical stimuli into biochemical signals via receptors, cytoskeletal networks and downstream signalling pathways.

Extracellular matrix (ECM): Three-dimensional network of proteins and polysaccharides that provides structural support and biochemical cues to cells.

Matrix stiffness: Measure of the rigidity of a material or tissue, often expressed in kilopascals, that influences cell adhesion, spreading and differentiation.

Macrophage polarisation: Spectrum of functional states adopted by macrophages in response to environmental cues, commonly described as pro-inflammatory (M1) or pro-regenerative (M2).

Dendritic cells: Antigen-presenting cells that bridge innate and adaptive immunity by capturing antigens in peripheral tissues and migrating to lymphoid organs to activate T cells.

References

1. Substrate stiffness influences phenotype and function of human antigen-presenting dendritic cells. Scientific Reports (2017).
2. Engineering Biomaterials to Model Immune‐Tumor Interactions In Vitro. Advanced Materials (2024).
3. Nanotube patterning reduces macrophage inflammatory response via nuclear mechanotransduction. Journal of Nanobiotechnology (2023).
4. CaMKK2 Regulates Macrophage Polarization Induced by Matrix Stiffness: Implications for Shaping the Immune Response in Stiffened Tissues. Advanced Science (2025).