Mechanotransduction: Forcing a change in metabolism

Mechanical activation of VE-cadherin stimulates AMPK to increase endothelial cell metabolism and vasodilation

“…The response of cells to mechanical cues requires increases in protein synthesis, transport, actomyosin contractility, and actin polymerization needed for the cell to counter the applied tension (Dawson, Cronin and DeMali, 2023). All these processes require energy.…”

“…Our observations that VE-cadherin increases AMPK activity in response to mechanical cues prompts investigation into the consequences of this activation. The cellular response to mechanical cues requires elevations in enzymatic activity, actin polymerization, and actomyosin contractility, all of which are energy-intensive processes necessary for cytoskeletal rearrangement and adhesion growth (Dawson, Cronin and DeMali, 2023). Given that glucose is the preferred energy source for endothelial cells, we hypothesized that the increase in AMPK activity due to VE-cadherin could enhance glucose metabolism.…”

“…How cells derive the energy they need to support reinforcement of the cell-cell adhesions and the actin cytoskeleton is an area of active investigation. In response to increases in tension, modifications to the enzymes and allosteric modulators involved in energy metabolism are altered (Dawson, Cronin and DeMali, 2023). In epithelial cells, E-cadherin senses external forces, the tension is propagated through the protein to produce conformational changes on the cytoplasmic domain (Borghi et al ., 2012).…”

“…Additionally, VE-cadherin only bears force when present in adherens junction (Conway et al ., 2013) This contrasts with E-cadherin, which bears force when it is on the cell surface and irrespective of its presence in adherens junctions (Borghi et al ., 2012). Finally, while both endothelial and epithelial cells heavily rely upon glycolysis to meet their energetic demands, endothelial cells have fewer mitochondria and do not employ oxidative phosphorylation to the same extent as epithelial cells to generate energy (Dawson, Cronin and DeMali, 2023). These observations raise the question as to how AMPK is activated in response to external forces in endothelial and the consequences of its activation.…”

Cellular elasticity in cancer: a review of altered biomechanical features

“…When combined, our findings show the value of sandwich culture platforms with stiffness gradients for investigating both adhesion-dependent and -independent cell migration, as well as for enhancing the variety of in vitro cancer metastasis models already available. [66][67][68][69] 2.1.3. Elasticity and cell metastasis.…”