Ageing modulates human dermal fibroblast contractility: quantification using nano-biomechanical testing

TY - JOUR

T1 - Ageing modulates human dermal fibroblast contractility: quantification using nano-biomechanical testing

AU - Yu, Zhuonan

AU - Smith, Matthew

AU - Siow, Richard

AU - Liu, Kuo-Kang

N1 - Funding Information: The authors thank Doctor Ken Mao, School of Engineering, University of Warwick, for helpful discussions and valuable suggestions during this research work. We would also like to thank Professor Giovanni Mann, School of Cardiovascular Medicine and Sciences, Faculty of Life Sciences & Medicine, King's College London, for scientific discussion and encouragement. This study was partly funded by Ageing Research at King's (ARK). Publisher Copyright: © 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4/5

Y1 - 2021/4/5

N2 - Dermal fibroblasts play a key role in maintaining homoeostasis and functionality of the skin. Their contractility plays a role in changes observed during ageing, especially in processes such as wound healing, inflammation, wrinkling and scar tissue formation as well as structural changes on extracellular matrix. Although alternations in skin physiology and morphology have been previously described, there remains a paucity of information about the influence of chronological ageing on dermal fibroblast contractility. In this study, we applied a novel nano-biomechanical technique on cell-embedded collagen hydrogels in combination with mathematical modelling and numerical simulation to measure contraction forces of normal human dermal fibroblasts (NHDF). We achieved quantitative differentiation of the contractility of cells derived from ‘young’ (< 30 years old) and ‘aged’ (> 60 years old) donors. Transforming growth factor β1 (TGF-β1) was used to stimulate the fibroblasts to assess their contractile potential. NHDF from aged donors exhibited a greater basal contractile force, while in contrast, NHDF from young donors have shown a significantly larger contractile force in response to TGF-β1 treatment. These findings validate our nano-biomechanical measurement technique and provide new insights for considering NHDF contractility in regenerative medicine and as a biomarker of dermal ageing processes.

AB - Dermal fibroblasts play a key role in maintaining homoeostasis and functionality of the skin. Their contractility plays a role in changes observed during ageing, especially in processes such as wound healing, inflammation, wrinkling and scar tissue formation as well as structural changes on extracellular matrix. Although alternations in skin physiology and morphology have been previously described, there remains a paucity of information about the influence of chronological ageing on dermal fibroblast contractility. In this study, we applied a novel nano-biomechanical technique on cell-embedded collagen hydrogels in combination with mathematical modelling and numerical simulation to measure contraction forces of normal human dermal fibroblasts (NHDF). We achieved quantitative differentiation of the contractility of cells derived from ‘young’ (< 30 years old) and ‘aged’ (> 60 years old) donors. Transforming growth factor β1 (TGF-β1) was used to stimulate the fibroblasts to assess their contractile potential. NHDF from aged donors exhibited a greater basal contractile force, while in contrast, NHDF from young donors have shown a significantly larger contractile force in response to TGF-β1 treatment. These findings validate our nano-biomechanical measurement technique and provide new insights for considering NHDF contractility in regenerative medicine and as a biomarker of dermal ageing processes.

KW - Ageing

KW - Cell mechanics

KW - COLLAGEN HYDROGEL

KW - Nanoindentation

KW - Force displacement

KW - TGF-β1

KW - Finite element

UR - http://www.scopus.com/inward/record.url?scp=85100271562&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.bbamcr.2021.118972

DO - https://doi.org/10.1016/j.bbamcr.2021.118972

M3 - Article

SN - 0167-4889

VL - 1868

JO - Biochimica et biophysica acta-Molecular cell research

JF - Biochimica et biophysica acta-Molecular cell research

IS - 5

M1 - 118972

ER -