TY - JOUR
T1 - Remodeling by fibroblasts alters the rate-dependent mechanical properties of collagen
AU - Babaei, Behzad
AU - Davarian, Ali
AU - Lee, Sheng Lin
AU - Pryse, Kenneth M.
AU - McConnaughey, William B.
AU - Elson, Elliot L.
AU - Genin, Guy M.
N1 - Publisher Copyright:
© 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - The ways that fibroblasts remodel their environment are central to wound healing, development of musculoskeletal tissues, and progression of pathologies such as fibrosis. However, the changes that fibroblasts make to the material around them and the mechanical consequences of these changes have proven difficult to quantify, especially in realistic, viscoelastic three-dimensional culture environments, leaving a critical need for quantitative data. Here, we observed the mechanisms and quantified the mechanical effects of fibroblast remodeling in engineered tissue constructs (ETCs) comprised of reconstituted rat tail (type I) collagen and human fibroblast cells. To study the effects of remodeling on tissue mechanics, stress-relaxation tests were performed on ETCs cultured for 24, 48, and 72 h. ETCs were treated with deoxycholate and tested again to assess the ECM response. Viscoelastic relaxation spectra were obtained using the generalized Maxwell model. Cells exhibited viscoelastic damping at two finite time constants over which the ECM showed little damping, approximately 0.2 s and 10-30 s. Different finite time constants in the range of 1-7000 s were attributed to ECM relaxation. Cells remodeled the ECM to produce a relaxation time constant on the order of 7000 s, and to merge relaxation finite time constants in the 0.5-2 s range into a single time content in the 1 s range. Results shed light on hierarchical deformation mechanisms in tissues, and on pathologies related to collagen relaxation such as diastolic dysfunction. Statement of Significance As fibroblasts proliferate within and remodel a tissue, they change the tissue mechanically. Quantifying these changes is critical for understanding wound healing and the development of pathologies such as cardiac fibrosis. Here, we characterize for the first time the spectrum of viscoelastic (rate-dependent) changes arising from the remodeling of reconstituted collagen by fibroblasts. The method also provides estimates of the viscoelastic spectra of fibroblasts within a three-dimensional culture environment. Results are of particular interest because of the ways that fibroblasts alter the mechanical response of collagen at loading frequencies associated with cardiac contraction in humans.
AB - The ways that fibroblasts remodel their environment are central to wound healing, development of musculoskeletal tissues, and progression of pathologies such as fibrosis. However, the changes that fibroblasts make to the material around them and the mechanical consequences of these changes have proven difficult to quantify, especially in realistic, viscoelastic three-dimensional culture environments, leaving a critical need for quantitative data. Here, we observed the mechanisms and quantified the mechanical effects of fibroblast remodeling in engineered tissue constructs (ETCs) comprised of reconstituted rat tail (type I) collagen and human fibroblast cells. To study the effects of remodeling on tissue mechanics, stress-relaxation tests were performed on ETCs cultured for 24, 48, and 72 h. ETCs were treated with deoxycholate and tested again to assess the ECM response. Viscoelastic relaxation spectra were obtained using the generalized Maxwell model. Cells exhibited viscoelastic damping at two finite time constants over which the ECM showed little damping, approximately 0.2 s and 10-30 s. Different finite time constants in the range of 1-7000 s were attributed to ECM relaxation. Cells remodeled the ECM to produce a relaxation time constant on the order of 7000 s, and to merge relaxation finite time constants in the 0.5-2 s range into a single time content in the 1 s range. Results shed light on hierarchical deformation mechanisms in tissues, and on pathologies related to collagen relaxation such as diastolic dysfunction. Statement of Significance As fibroblasts proliferate within and remodel a tissue, they change the tissue mechanically. Quantifying these changes is critical for understanding wound healing and the development of pathologies such as cardiac fibrosis. Here, we characterize for the first time the spectrum of viscoelastic (rate-dependent) changes arising from the remodeling of reconstituted collagen by fibroblasts. The method also provides estimates of the viscoelastic spectra of fibroblasts within a three-dimensional culture environment. Results are of particular interest because of the ways that fibroblasts alter the mechanical response of collagen at loading frequencies associated with cardiac contraction in humans.
KW - Collagen
KW - Human dermal fibroblasts
KW - Remodeling
KW - Viscoelasticity
UR - http://www.scopus.com/inward/record.url?scp=84962045927&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2016.03.034
DO - 10.1016/j.actbio.2016.03.034
M3 - Article
C2 - 27015891
AN - SCOPUS:84962045927
SN - 1742-7061
VL - 37
SP - 28
EP - 37
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -