Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis

Júnior, Constança; Narciso, Maria; Marhuenda, Esther; Almendros, Isaac; Farré, Ramon; Navajas, Daniel; Otero, Jorge; Gavara, Núria

doi:10.3390/ijms222312928

Open AccessArticle

Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis

by

Constança Júnior

^1,2

,

Maria Narciso

^1,2

,

Esther Marhuenda

^1,3,4

,

Isaac Almendros

^1,3,4

,

Ramon Farré

^1,3,4

,

Daniel Navajas

^1,2,3,

Jorge Otero

^1,2,3 and

Núria Gavara

^1,2,*

¹

Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain

²

The Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain

³

CIBER de Enfermedades Respiratorias, 28029 Madrid, Spain

⁴

Institut d’Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(23), 12928; https://doi.org/10.3390/ijms222312928

Submission received: 2 November 2021 / Revised: 23 November 2021 / Accepted: 25 November 2021 / Published: 29 November 2021

(This article belongs to the Special Issue Mechanical and Biochemical Interplay between Cells and Their Microenvironment)

Download

Browse Figures

Versions Notes

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.

Keywords: extracellular matrix; atomic force microscopy; mechanosensing; fibrosis

Share and Cite

MDPI and ACS Style

Júnior, C.; Narciso, M.; Marhuenda, E.; Almendros, I.; Farré, R.; Navajas, D.; Otero, J.; Gavara, N. Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis. Int. J. Mol. Sci. 2021, 22, 12928. https://doi.org/10.3390/ijms222312928

AMA Style

Júnior C, Narciso M, Marhuenda E, Almendros I, Farré R, Navajas D, Otero J, Gavara N. Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis. International Journal of Molecular Sciences. 2021; 22(23):12928. https://doi.org/10.3390/ijms222312928

Chicago/Turabian Style

Júnior, Constança, Maria Narciso, Esther Marhuenda, Isaac Almendros, Ramon Farré, Daniel Navajas, Jorge Otero, and Núria Gavara. 2021. "Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis" International Journal of Molecular Sciences 22, no. 23: 12928. https://doi.org/10.3390/ijms222312928

APA Style

Júnior, C., Narciso, M., Marhuenda, E., Almendros, I., Farré, R., Navajas, D., Otero, J., & Gavara, N. (2021). Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis. International Journal of Molecular Sciences, 22(23), 12928. https://doi.org/10.3390/ijms222312928

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI