The shear stress of it all: the cell membrane and mechanochemical transduction
Open accessAbstract
As the inner lining of the vessel wall, vascular endothelial cells are poised to act as a signal transduction interface between haemodynamic forces and the underlying vascular smooth-muscle cells. Detailed analyses of fluid mechanics in atherosclerosis-susceptible regions of the vasculature reveal a strong correlation between endothelial cell dysfunction and areas of low mean shear stress and oscillatory flow with flow recirculation. Conversely, steady shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. The molecular basis of shear-induced mechanochemical signal transduction and the endothelium's ability to discriminate between flow profiles remains largely unclear. Given that fluid shear stress does not involve a traditional receptor/ligand interaction, identification of the molecule(s) responsible for sensing fluid flow and mechanical force discrimination has been difficult. This review will provide an overview of the haemodynamic forces experienced by the vascular endothelium and its role in localizing atherosclerotic lesions within specific regions of the vasculature. Also reviewed are several recent lines of evidence suggesting that both changes in membrane microviscosity linked to heterotrimeric G proteins, and the transmission of tension across the cell membrane to the cell–cell junction where known shear-sensitive proteins are localized, may serve as the primary force-sensing elements of the cell.
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Stem cells sense active and passive forces from their external microenvironment and convert these physical stimuli into biochemical responses.
“it is now increasingly appreciated that stem cells also experience active and passive forces from their external microenvironment and convert these physical stimuli into biochemical responses19.”
From Organoids (2022) · cites this paper as [19]
The section headed “Do changes in membrane fluidity modulate mechanochemical signal transduction?” describes cells converting mechanical stimuli into biochemical signals. The review discusses this process in endothelial cells, however; it does not establish the claim specifically for stem cells or distinguish active and passive forces in their microenvironment. (LLM, conf=0.88)
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“The mechanisms that modulate cell behaviour by fluid shear stress is diverse, but is mediated primarily through cell surface receptors (Tzima et al. 2001), cell adhesion molecules (Tzima et al. 2005) and heterodimeric G proteins (White and Frangos 2007).”
BackgroundResponse of cells and tissues to shear stress
Espina, J. A., Cordeiro, M. H., Milivojevic, M. S., Pajić‐Lijaković, I., & Barriga, E. H. (2023) · Journal of Cell Science · doi:10.1242/jcs.260985 · Cited by 117 · see citing works
“Thus, it has been speculated that the first step of the mechanosensitive response to shear stress arises from changes in membrane fluidity, leading to activation of G proteins (White and Frangos, 2007).”
The Role of the Transcription Factor KLF2 in Vascular Development and Disease
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“Fluid shear stress does not involve traditional receptor/ ligand binding, therefore, identifying the molecules that sense shear stress has been difficult (White and Frangos, 2007).”
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“Remodelling of the phospholipid bilayer can occur few seconds after onset of shear stress with potential alteration of the protein organization and activity resulting in downstream activation of signalling pathways.(59) Several ion channels including K, Na, Ca, TRPV (transient receptor potential cation channel) and Pi…”
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“Because many types of cells have mechanosensitive membrane receptors that are sensitive to shear stress (27), a large off-axis angle means the cellular contraction force in the normal direction may activate these shear-sensing receptors as well.”
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“In case of liver microvasculature, despite the low flow rate of blood, the narrow capillary diameter results in a significant shear stress generation [49, 50].”
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“Mechanical stimulation, a shear stress in particular, is also thought play an important role in modulation of the tissue-specific function [88, 89 ].”
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“Ion channels [22], focal adhesion complex [23], glycocalyx [24], platelet-endothelial cellular adhesion molecules (PECAM)-1[21], and G protein-coupled receptors [25] are now thought to be involved in the sensing of SS by ECs.”
BackgroundRheology, simulation and data analysis toward bioprinting cell viability awareness
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“In vitro systems designed to expose EC to controlled levels of fluid shear stress (SS) have greatly advanced our understanding of the molecular mechanisms underlying the transduction of hemodynamic shear stress into biological signals.[2,27] It is now recognized that specific details of the shear waveform have importa…”
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“The cell membrane lipid bilayer itself may serve as a mechanotransducer (White and Frangos, 2007).”
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“Consequently, a steady or unsteadyWSS within the vasculature plays a vital role in the long-term health of the blood vessels.(15,16) A WSS assessment in clinical practice may be helpful in the analysis of diverse pathophysiologic conditions.”
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“Physiological flow shear stress (10–25 dyn/cm 2 ) serves as an important regulator of pathophysiologically relevant gene expression in endothelial cells [ , , ,”
A critical appraisal of the hemodynamic signal driving liver regeneration
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“protein-coupled receptors (GPCRs) [144-146].”
Mechanical Induction of Gene Expression in Connective Tissue Cells
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“Indeed, pulsatile flow typical of a normal cardiac cycle has been shown to trigger rapid and sustained NO production (White and Frangos, 2007).”
BackgroundShear stress and VEGF enhance endothelial differentiation of human adipose-derived stem cells
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“The shear stress of circulating blood is very low in these areas of the liver and the StabilinStabilins may immobilize these dead/dying cells for engulfment by Kupffer cells [19,53,54].”
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“The localization of the Gαq/11–PECAM-1 complex to the endothelial cell–cell junction positions this mechanosensor complex to a region of greatest shear-induced mechanical tension (Fung & Liu, 1993; White & Frangos, 2007).”
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“This finding is consistent with previous literature reports: the presence of high and low WSS values is usually accompanied by complex flow conditions (16, 31).”
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- Authors
- White, C. R., & Frangos, J. A.
- Affiliations
- La Jolla Bioengineering Institute (US)
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2007-06-14
- Volume
- 362
- Issue
- 1484
- Pages
- 1459-1467
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC2440408
- OpenAlex
- W2135425711
- Cited by
- 255
- References
- 67
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 15 · 2023: 14 · 2022: 11 · 2021: 19 · 2020: 21 · 2019: 13 · 2018: 9 · 2017: 14 · 2016: 16 · 2015: 15 · 2014: 16 · 2013: 13 · 2012: 12
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r37hl040696-32)
- National Heart, Lung, and Blood Institute (R01HL040696, R37-HL-040696, HL40696)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- fluid shear stress, vascular endothelium, atherosclerosis, hemodynamic forces, oscillatory flow, recirculating flow, endothelial dysfunction, membrane microviscosity, heterotrimeric G proteins, cell-cell contact, atheroprotection, mechanosensing
- MeSH terms
- Biomechanical Phenomena, Blood Circulation, Cell Membrane, Mechanotransduction, Cellular, Endothelial Cells
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