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The effect of time-dependent deformation of viscoelastic hydrogels on myogenic induction and Rac1 activity in mesenchymal stem cells

Overview of attention for article published in Clinical Materials, December 2013
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Title
The effect of time-dependent deformation of viscoelastic hydrogels on myogenic induction and Rac1 activity in mesenchymal stem cells
Published in
Clinical Materials, December 2013
DOI 10.1016/j.biomaterials.2013.11.023
Pubmed ID
Authors

Andrew R. Cameron, Jessica E. Frith, Guillermo A. Gomez, Alpha S. Yap, Justin J. Cooper-White

Abstract

Cell behaviours within tissues are influenced by a broad array of physical and biochemical microenvironmental factors. Whilst 'stiffness' is a recognised physical property of substrates and tissue microenvironments that influences many cellular behaviours, tissues and their extracellular matrices are not purely rigid but 'viscoelastic' materials, composed of both rigid-like (elastic) and dissipative (viscous) elements. This viscoelasticity results in materials displaying increased deformation with time under the imposition of a defined force or stress, a phenomenon referred to as time-dependent deformation or 'creep'. Previously, we compared the behaviour of human mesenchymal stem cells (hMSCs) on hydrogels tailored to have a constant stiffness, but to display varying levels of creep in response to an applied force. Using polyacrylamide as a model material, we showed that on high-creep hydrogels (HCHs), hMSCs displayed increased proliferation, spread area and differentiation towards multiple lineages, compared to their purely stiff analogue, with a particular propensity for differentiation towards a smooth muscle cell (SMC) lineage. In this present study, we investigate the mechanisms behind this phenomenon and show that hMSCs adhered to HCHs have increased expression of SMC induction factors, including soluble factors, ECM proteins and the cell-cell adhesion molecule, N-Cadherin. Further, we identify a key role for Rac1 signalling in mediating this increased N-Cadherin expression. Using a real-time Rac1-FRET biosensor, we confirm increased Rac1 activation on HCHs, an observation that is further supported functionally by observed increases in motility and lamellipodial protrusion rates of hMSCs. Increased Rac1 activity in hMSCs on HCHs provides underlying mechanisms for enhanced commitment towards a SMC lineage and the compensatory increase in spread area (isotonic tension) after a creep-induced loss of cytoskeletal tension on viscoelastic substrates, in contrast to previous studies that have consistently demonstrated up-regulation of RhoA activity with increasing substrate stiffness. Tuning substrate viscoelasticity to introduce varying levels of creep thus equips the biomaterial scientist or engineer with a new tool with which to tune and direct stem cell outcomes.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 191 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 1%
United States 2 1%
Ireland 1 <1%
Germany 1 <1%
Unknown 185 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 56 29%
Researcher 24 13%
Student > Master 18 9%
Student > Bachelor 14 7%
Professor 11 6%
Other 28 15%
Unknown 40 21%
Readers by discipline Count As %
Engineering 43 23%
Materials Science 26 14%
Agricultural and Biological Sciences 25 13%
Biochemistry, Genetics and Molecular Biology 15 8%
Chemistry 9 5%
Other 28 15%
Unknown 45 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 October 2019.
All research outputs
#16,063,069
of 25,394,764 outputs
Outputs from Clinical Materials
#8,839
of 10,758 outputs
Outputs of similar age
#189,010
of 320,422 outputs
Outputs of similar age from Clinical Materials
#109
of 134 outputs
Altmetric has tracked 25,394,764 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 10,758 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one is in the 16th percentile – i.e., 16% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 320,422 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 134 others from the same source and published within six weeks on either side of this one. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.