首页|Piezol Response to Shear Stress Is Controlled by the Components of the Extracellular Matrix

Piezol Response to Shear Stress Is Controlled by the Components of the Extracellular Matrix

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Piezol is a recently discovered Ca~(2+) permeable ion channel that has emerged as an integral sensor of hemodynamic forces within the cardiovascular system,contributing to vascular development and blood pressure regulation.However,how the composition of the extracellular matrix(ECM) affects the mechanosensitivity of Piezol in response to hemodynamic forces remains poorly understood.Using a combination of microfluidics and calcium imaging techniques,we probe the shear stress sensitivity of single HEK293T cells engineered to stably express Piezol in the presence of different ECM proteins.Our experiments show that Piezol sensitivity to shear stress is not dependent on the presence of ECM proteins.However,different ECM proteins regulate the sensitivity of Piezol depending on the shear stress level.Under high shear stress,fibronectin sensitizes Piezol response to shear,while under low shear stress,Piezol mechanosensitivity is improved in the presence of collagen types I and IV and laminin.Moreover,we report that α5β1 and αvβ3 integrins are involved in Piezol sensitivity at high shear,while αvβ3 and αvβ5 integrins are involved in regulating the Piezol response at low shear stress.These results demonstrate that the ECM/integrin interactions influence Piezol mechanosensitivity and could represent a mechanism whereby extracellular forces are transmitted to Piezol channels,providing new insights into the mechanism by which Piezol senses shear stress.

Piezolshear stressmechanotransductionextracellular matrixintegrins

Austin Lai、Peter Thurgood、Charles D.Cox

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School of Health & Biomedical Sciences,RMIT University,Bundoora,Victoria 3082,Australia

School of Engineering,RMIT University,Melbourne,Victoria 3000,Australia

Molecular Cardiology and Biophysics Division,Victor Chang Cardiac Research Institute,Sydney,New South Wales 2010,Australia

2022

10.1021/acsami.2c09169

ACS applied materials & interfaces

ACS applied materials & interfaces

SCI
ISSN：1944-8244
年,卷(期)：2022.14(36)
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