The mechanical memory of lung myofibroblasts

2012 ◽  
Vol 4 (4) ◽  
pp. 410 ◽  
Author(s):  
Jenna L. Balestrini ◽  
Sidharth Chaudhry ◽  
Vincent Sarrazy ◽  
Anne Koehler ◽  
Boris Hinz
Keyword(s):  
Mechanical Memory

scholarly journals Decreased Substrate Stiffness Promotes a Hypofibrotic Phenotype in Cardiac Fibroblasts

2021 ◽  
Vol 22 (12) ◽  
pp. 6231
Author(s):  
Rachel C. Childers ◽  
Pamela A. Lucchesi ◽  
Keith J. Gooch
Keyword(s):  
Nuclear Translocation ◽  
Cardiac Fibroblasts ◽  
Volume Overload ◽  
Substrate Stiffness ◽  
Aortocaval Fistula ◽  
Failure Model ◽  
Tissue Stiffness ◽  
Mechanical Memory ◽  
Heart Failure Model ◽  
Control Sham

A hypofibrotic phenotype has been observed in cardiac fibroblasts (CFs) isolated from a volume overload heart failure model, aortocaval fistula (ACF). This paradoxical phenotype results in decreased ECM synthesis despite increased TGF-β presence. Since ACF results in decreased tissue stiffness relative to control (sham) hearts, this study investigates whether the effects of substrate stiffness could account for the observed hypofibrotic phenotype in CFs isolated from ACF. CFs isolated from ACF and sham hearts were plated on polyacrylamide gels of a range of stiffness (2 kPa to 50 kPa). Markers related to cytoskeletal and fibrotic proteins were measured. Aspects of the hypofibrotic phenotype observed in ACF CFs were recapitulated by sham CFs on soft substrates. For instance, sham CFs on the softest gels compared to ACF CFs on the stiffest gels results in similar CTGF (0.80 vs. 0.76) and transgelin (0.44 vs. 0.57) mRNA expression. The changes due to stiffness may be explained by the observed decreased nuclear translocation of transcriptional regulators, MRTF-A and YAP. ACF CFs appear to have a mechanical memory of a softer environment, supported by a hypofibrotic phenotype overall compared to sham with less YAP detected in the nucleus, and less CTGF and transgelin on all stiffnesses.

scholarly journals Heterogeneity in The Mechanical Properties of Integrins Determines Mechanotransduction Dynamics in Bone Osteoblasts

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aban Shuaib ◽  
Daniyal Motan ◽  
Pinaki Bhattacharya ◽  
Alex McNabb ◽  
Timothy M. Skerry ◽  
...  
Keyword(s):  
Mechanical Stimulation ◽  
Bone Cells ◽  
Multiscale Model ◽  
Cellular Responses ◽  
Mechanical Adaptation ◽  
Mechanical Responses ◽  
Tissue Interactions ◽  
Model Combining ◽  
Mechanical Memory ◽  
Dynamic Interplay

Abstract Bone cells are exposed to dynamic mechanical stimulation that is transduced into cellular responses by mechanotransduction mechanisms. The extracellular matrix (ECM) provides a physical link between loading and bone cells, where mechanoreceptors, such as integrins, initiate mechanosensation. Though this relationship is well studied, the dynamic interplay between mechanosensation, mechanotransduction and cellular responses is unclear. A hybrid-multiscale model combining molecular, cellular and tissue interactions was developed to examine links between integrins’ mechanosensation and effects on mechanotransduction, ECM modulation and cell-ECM interaction. The model shows that altering integrin mechanosensitivity threshold (MT) increases mechanotransduction durations from hours to beyond 4 days, where bone formation starts. This is relevant to bone, where it is known that a brief stimulating period provides persistent influences for over 24 hours. Furthermore, the model forecasts that integrin heterogeneity, with respect to MT, would be able to induce sustained increase in pERK baseline > 15% beyond 4 days. This is analogous to the emergence of molecular mechanical memory signalling dynamics. Therefore, the model can provide a greater understanding of mechanical adaptation to differential mechanical responses at different times. Given reduction of bone sensitivity to mechanical stimulation with age, these findings may lead towards useful therapeutic targets for upregulation of bone mass.

Mechanics-Controlled Dynamic Cell Niches Guided Osteogenic Differentiation of Stem Cells via Preserved Cellular Mechanical Memory

2019 ◽  
Vol 12 (1) ◽  
pp. 260-274 ◽  
Author(s):  
Dan Wei ◽  
Amin Liu ◽  
Jing Sun ◽  
Suping Chen ◽  
Chengheng Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Dynamic Cell ◽  
Mechanical Memory

scholarly journals Mechanical memory and dosing influence stem cell fate

2014 ◽  
Vol 13 (6) ◽  
pp. 645-652 ◽  
Author(s):  
Chun Yang ◽  
Mark W. Tibbitt ◽  
Lena Basta ◽  
Kristi S. Anseth
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Fate ◽  
Mechanical Memory
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