Mechanobiology of Endothelial Cell Interactions and Responses

Mechanobiology of the endothelium examines how physical forces and extracellular mechanics influence the behaviour, structure and function of vascular endothelial cells. These cells form a dynamic monolayer that lines blood and lymph vessels, sensing shear stress from blood flow, cyclic stretch, substrate stiffness and osmotic forces. Mechanical cues are detected by specialised structures including cell–cell junctions, focal adhesions and the glycocalyx, which transduce forces into biochemical signals to regulate barrier integrity, migration, proliferation and inflammatory responses. Homeostatic shear stress promotes junctional stability, anti-inflammatory signalling and barrier maintenance, whereas disturbed or oscillatory flow leads to junctional remodelling, endothelial dysfunction and atheroprone phenotypes. Substrate stiffness modulates cell traction forces and cytoskeletal organisation, often independently of transcriptional changes, guiding angiogenesis and vascular remodelling. Osmotic challenges and metabolic stresses further interact with mechanosensitive pathways, altering endothelial mechanics via regulators such as small GTPases. Advances in computational modelling, microphysiological systems and in vitro flow devices have deepened understanding of endothelial mechanotransduction, revealing potential therapeutic targets to restore vascular barrier function and mitigate disease progression.

Research from Nature Portfolio

One foundational study developed a computational fluid dynamics–based in vitro model to replicate disturbed flow patterns around irregular plaque geometries. Exposure to low shear and swirling flow induced endothelial morphological changes, cytoskeletal reorganisation, increased reactive oxygen species and pro-inflammatory marker expression, closely mirroring early atherosclerotic microenvironments. This model offers a versatile platform for probing mechanotransduction under pathophysiological flow. Another key investigation compared endothelial monolayers on substrates of differing stiffness, measuring cell–matrix traction forces and transcriptome profiles. While stiffer substrates elicited higher traction stresses and activation of mechanosensitive signalling via transforming growth factor-β2, genome-wide expression remained largely unchanged, demonstrating that endothelial mechanical adaptation can occur independently of transcriptional reprogramming.

Mechanobiology of Endothelial Cell Interactions and Responses publication trend

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

Technical terms

Mechanotransduction: The process by which cells convert mechanical stimuli into biochemical signals.

Shear stress: Frictional force exerted by blood flow on the endothelial surface.

Substrate stiffness: Mechanical rigidity of the extracellular matrix or culture substrate experienced by cells.

Traction force: Contractile force exerted by cells on their substrate through focal adhesions.

Hyperosmolarity: Elevated osmotic concentration in the extracellular environment.

Cdc42: A small GTPase that regulates cytoskeletal dynamics and cell mechanics.

Endothelial-cadherin: A cell–cell adhesion protein critical for vascular barrier integrity.

References

1. Mechanobiological Adaptation to Hyperosmolarity Enhances Barrier Function in Human Vascular Microphysiological System. Advanced Science (2023).
2. Biodegradable polymeric nanoparticles increase risk of cardiovascular diseases by inducing endothelium dysfunction and inflammation. Journal of Nanobiotechnology (2023).
3. Vascular endothelial cellular mechanics under hyperglycemia and its role in tissue regeneration. Regenerative Biomaterials (2024).
4. Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques. Scientific Reports (2016).
5. Subendothelial stiffness alters endothelial cell traction force generation while exerting a minimal effect on the transcriptome. Scientific Reports (2019).