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Title: Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis
Author: Júnior, Constança
Narciso, Maria
Marhuenda, Esther
Almendros López, Isaac
Farre, Ramon
Navajas Navarro, Daniel
Otero Díaz, Jorge
Gavara i Casas, Núria
Keywords: Fibrosi pulmonar
Microscòpia de força atòmica
Pulmonary fibrosis
Atomic force microscopy
Issue Date: 29-Nov-2021
Publisher: MDPI AG
Abstract: Pulmonary fibrosis (PF) is a progressive disease that disrupts the mechanical homeostasis of the lung extracellular matrix (ECM). These effects are particularly relevant in the lung context, given the dynamic nature of cyclic stretch that the ECM is continuously subjected to during breathing. This work uses an in vivo model of pulmonary fibrosis to characterize the macro- and micromechanical properties of lung ECM subjected to stretch. To that aim, we have compared the micromechanical properties of fibrotic ECM in baseline and under stretch conditions, using a novel combination of Atomic Force Microscopy (AFM) and a stretchable membrane-based chip. At the macroscale, fibrotic ECM displayed strain-hardening, with a stiffness one order of magnitude higher than its healthy counterpart. Conversely, at the microscale, we found a switch in the stretch-induced mechanical behaviour of the lung ECM from strain-hardening at physiological ECM stiffnesses to strain-softening at fibrotic ECM stiffnesses. Similarly, we observed solidification of healthy ECM versus fluidization of fibrotic ECM in response to stretch. Our results suggest that the mechanical behaviour of fibrotic ECM under stretch involves a potential built-in mechanotransduction mechanism that may slow down the progression of PF by steering resident fibroblasts away from a pro-fibrotic profile.
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It is part of: International Journal Of Molecular Sciences, 2021, vol. 22
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ISSN: 1422-0067
Appears in Collections:Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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