Mechanotransduction in Soft Biological Tissues

Mechanotransduction describes the processes by which soft tissues perceive, transmit and respond to mechanical forces across multiple scales. In these tissues, specialised membrane proteins and focal adhesion complexes convert external stresses into intracellular biochemical signals. Those signals propagate through the cytoskeleton and extracellular matrix, guiding cell behaviour from migration and proliferation to differentiation and remodelling. Such mechanosensitive pathways underpin embryonic development, tissue homeostasis and repair, and their dysregulation contributes to fibrosis, vascular disease and impaired wound healing. Recent advances have emphasised the importance of three-dimensional context, revealing that cells in multicellular constructs exhibit distinct patterns of strain softening, cytoskeletal remodelling and matrix adaptation compared to monolayers. Understanding these dynamics offers routes to engineer functional tissue equivalents and to target mechanobiological pathways in disease.

Research from Nature Portfolio

One study introduced optogenetically modified fibroblasts embedded in collagen microtissues and used light to drive local RhoA‐mediated contractions. By measuring stress and strain in real time, researchers quantified tissue elasticity, strain propagation and the emergence of mechanical anisotropy, providing a non‐destructive toolkit to guide tissue formation. Another investigation developed a high‐throughput platform for probing dynamic mechanical properties and subcellular architecture in three‐dimensional microtissues of fibroblasts and muscle cells. It demonstrated that, under cyclic stretch, these constructs strain‐soften without fluidising and regain their prestress upon unloading, linking actin polymerisation dynamics to maintenance of a constant mean tension. A combined experimental and modelling effort examined engineered smooth muscle microtissues subjected to stretch–unstretch cycles. The work revealed that active actomyosin contractility masks the plastic deformation of the collagen–fibrin matrix, highlighting the interplay between cellular mechanics and matrix viscoplasticity in regulating tissue dynamics.

Mechanotransduction in Soft Biological Tissues publication trend

The graph below shows the total number of articles in mechanotransduction in soft biological tissues across all publications each year (not limited to Nature Index journals).

Technical terms

Mechanotransduction: Conversion of mechanical forces into intracellular biochemical signals that regulate cell function.

Extracellular matrix: Network of proteins and polysaccharides providing structural and biochemical support to cells.

Cytoskeleton: Dynamic filamentous network (actin, microtubules, intermediate filaments) that transmits forces and maintains cell shape.

Viscoplasticity: Material behaviour combining time‐dependent (viscous) and permanent (plastic) deformation under load.

Piezo1 channel: Mechanically activated ion channel that mediates calcium influx in response to membrane tension.

References

1. Light-driven biological actuators to probe the rheology of 3D microtissues. Nature Communications (2023).
2. Structural and mechanical remodeling of the cytoskeleton maintains tensional homeostasis in 3D microtissues under acute dynamic stretch. Scientific Reports (2020).
3. Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling. Scientific Reports (2016).
4. Aging‐associated decline in vascular smooth muscle cell mechanosensation is mediated by Piezo1 channel. Aging Cell (2023).
5. Mechanical homeostasis in tissue equivalents: a review. Biomechanics and Modeling in Mechanobiology (2021).
6. Collagen Fibrils Mechanically Contribute to Tissue Contraction in an In Vitro Wound Healing Scenario. Advanced Science (2019).