The importance of shear stress in biology

Understanding the importance of shear stress in biology is essential for unraveling how mechanical forces influence cellular behavior, tissue development, and disease progression. For example, up to 60% of the human adult body is water. This water is stored both within and outside the cells, constituting what are known as intracellular and extracellular fluids. Specifically, the extracellular fluids can be classified into interstitial fluid, contained within the extracellular matrix that surrounds cells in tissues, and blood plasma. Additionally, other water-based extracellular fluids include lymph, cerebrospinal fluid, synovial, pleural, pericardial, peritoneal, and ocular fluid.

Wherever fluid is present, shear stress will naturally occur as well. In particular, in biological and vascular processes, fluids act on the cell surface. For instance, blood flow exerts a frictional force called shear stress on the endothelium surface of vessel walls. Consequently, this mechanical phenomenon significantly impacts tissue function and biological responses through mechanotransduction processes. Furthermore, it modulates cell morphology, proliferation, differentiation, metabolism, communication, and aids in barrier formation[1]. Then, what is exactly shear stress?

Shear stress (Ʈ) is defined as a mechanical force exerted when a tangential force (F) acts on a surface (area = A):

Ʈ=F/A

For a Newtonian fluid, with constant viscosity, the shear stress depends on the viscosity (ɳ) and the shear rate ( dv/dz)

Ʈ= ɳ(dv/dz)

Although shear stress unit in the IS system is Pascal (Pa), for the cardiovascular system and biological applications shear stress is measured in dyne/cm². Being 1 Pa = 10 dynes/cm².

Shear stress on endothelial cells

Many cell types are constantly subjected to fluid shear stress. For instance, endothelial cells from vascular blood vessels and the lymphatic system are exposed to circulating blood and lymph. Depending on the vessel type, shear stress may vary from 30 dynes/cm² in arteries to 1 dyne/cm² in venous vessels and capillaries[2]. Researchers have shown that endothelial shear stress actively alters cytoskeletal organization, reshapes cells, and changes gene expression. It also increases intracellular calcium concentrations, triggers nitric oxide production, and induces actin stress fiber formation, aligning and remodelling the microfilament network in the flow’s direction[3,4].

Shear stress on epithelial cells

Similarly, epithelial cells from different tissues are also exposed to shear stress forces. The kidney, in its filtering function through a sophisticated tubular network, is capable of filtrating 120 ml per minute, which means 180 L per day[5]. Therefore epithelial cells lining every nephron are exposed to the shear stress of glomerular filtrate, estimated between 0.1-1 dyne/cm². Some studies have demonstrated that renal proximal tubule epithelial cells lead to cilia formation in the presence of shear stress. In addition, the mediated signal transduction is regulated, improving epithelial cytoarchitecture, leading to increased cell volume, and greater polarization of aquaporins, cation transporters and ion channels than kidney epithelial cells in static culture[6].

Shear stress from airflow

The blood vessels surrounding alveoli of the lung are continuously exposed to shear stress from blood flow. However, shear stress is also generated on the air side of the alveolar-capillary barrier. At every breath, epithelial cells lining our airways are exposed to shear stress generated by the airflow, which at rest breathing is 0.5-3 dynes/cm². These forces have been demonstrated to modulate airway epithelial barrier function, mucous production and ciliary beating alignment[3,7].

Shear stress from peristaltic motion

Also, in the human intestinal tract, the flow of digesta induced by the peristaltic motion of the intestinal wall affects the enterocytes lining the digestive tube, which has been previously shown to be 0.002-0.08 dynes/cm². Gut-on-a-chip microdevices applying fluid flow and shear stress promotes accelerated intestinal epithelial cell differentiation, formation of 3D villi-like structures, and increased intestinal barrier function, recapitulating many complex functions of the normal human intestine[8].

It seems clear that shear stress plays a key role in the function of tissues and organs. Microfluidic devices, unlike previous in vitro cell culture platforms, are considered a powerful tool that allows flow and shear stress control in situ. Hence, this technology increases the chances of developing reliable organ models for drug screening and toxicology testing.

Authors

This article has been written by Sandra González Lana.

Bibliography

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