Mesenchymal stem cells (MSCs) are a promising cell source for tissue engineering applications, given their ease of isolation and multi-potential differentiation capacity [1]. Passive and active mechanical signals can direct MSC lineage commitment [2], however, the subcellular machinery that translates physical cues to biologic response remains unclear. Direct deformation of the nucleus may influence differentiation by inducing mechanical reorganization of nuclear chromatin. Because the nuclei of differentiated cells are stiffer than progenitor cells [3], it is possible that such mechanoregulatory mechanisms vary with differentiation state. Lamin A/C is a filamentous protein that largely defines nuclear shape, size and stiffness [3]. Recent work suggests that Lamin A/C also regulates chromatin organization and transcriptional activity [4]. Recently, we have developed an in vitro system to direct the functional differentiation of MSCs into fibrochondrocytes, using electrospun polymeric nanofiber substrates [5]. Alignment of nanofibers directs cell alignment, allowing external forces to be applied uniformly along the long axes of cells, emulating the mechanical microenvironment experienced by embryonic progenitors during fibrous tissue morphogenesis [6]. We have noted, however, that as MSCs undergo fibrochondrogenesis, translation of scaffold deformation to nuclear deformation is attenuated [7]. From those studies, it was not clear whether this was due to changes in cellular mechanics or to accretion of extracellular matrix during differentiation. Thus the objective of the present work was to specifically identify how fibrochondrogenesis of MSCs on aligned nanofibrous scaffolds alters nuclear mechanics and mechanoreception, and further to ascertain whether mechanical stimulation alone can elicit similar mechanoregulatory changes.
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ASME 2011 Summer Bioengineering Conference
June 22–25, 2011
Farmington, Pennsylvania, USA
Conference Sponsors:
- Bioengineering Division
ISBN:
978-0-7918-5458-7
PROCEEDINGS PAPER
Differentiation and Dynamic Tensile Loading Alter Nuclear Mechanics and Mechanoreception in Mesenchymal Stem Cells
Su-Jin Heo,
Su-Jin Heo
University of Pennsylvania, Philadelphia, PA
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Nandan L. Nerurkar,
Nandan L. Nerurkar
University of Pennsylvania, Philadelphia, PA
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Tristan P. Driscoll,
Tristan P. Driscoll
University of Pennsylvania, Philadelphia, PA
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Robert L. Mauck
Robert L. Mauck
University of Pennsylvania, Philadelphia, PA
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Su-Jin Heo
University of Pennsylvania, Philadelphia, PA
Nandan L. Nerurkar
University of Pennsylvania, Philadelphia, PA
Tristan P. Driscoll
University of Pennsylvania, Philadelphia, PA
Robert L. Mauck
University of Pennsylvania, Philadelphia, PA
Paper No:
SBC2011-53432, pp. 323-324; 2 pages
Published Online:
July 17, 2013
Citation
Heo, S, Nerurkar, NL, Driscoll, TP, & Mauck, RL. "Differentiation and Dynamic Tensile Loading Alter Nuclear Mechanics and Mechanoreception in Mesenchymal Stem Cells." Proceedings of the ASME 2011 Summer Bioengineering Conference. ASME 2011 Summer Bioengineering Conference, Parts A and B. Farmington, Pennsylvania, USA. June 22–25, 2011. pp. 323-324. ASME. https://doi.org/10.1115/SBC2011-53432
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