A. James Clark School of Engineering

Permanent URI for this communityhttp://hdl.handle.net/1903/1654

The collections in this community comprise faculty research works, as well as graduate theses and dissertations.

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    Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent
    (MDPI, 2019-05-08) Doolin, Mary T.; Ornstein, Thea S.; Stroka, Kimberly M.
    Mechanosensing of the mechanical microenvironment by cells regulates cell phenotype and function. The nucleus is critical in mechanosensing, as it transmits external forces from the cellular microenvironment to the nuclear envelope housing chromatin. This study aims to elucidate how mechanical confinement affects nuclear deformation within several cell types, and to determine the role of cytoskeletal elements in controlling nuclear deformation. Human cancer cells (MDA-MB-231), human mesenchymal stem cells (MSCs), and mouse fibroblasts (L929) were seeded within polydimethylsiloxane (PDMS) microfluidic devices containing microchannels of varying cross-sectional areas, and nuclear morphology and volume were quantified via image processing of fluorescent cell nuclei. We found that the nuclear major axis length remained fairly constant with increasing confinement in MSCs and MDA-MB-231 cells, but increased with increasing confinement in L929 cells. Nuclear volume of L929 cells and MSCs decreased in the most confining channels. However, L929 nuclei were much more isotropic in unconfined channels than MSC nuclei. When microtubule polymerization or myosin II contractility was inhibited, nuclear deformation was altered only in MSCs in wide channels. This work informs our understanding of nuclear mechanics in physiologically relevant spaces, and suggests diverging roles of the cytoskeleton in regulating nuclear deformation in different cell types.
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    UTILIZATION OF PNEUMATIC ARTIFICIAL MUSCLES TO STUDY EFFECTS OF LOAD HISTORY ON THE INTERVERTEBRAL DISC
    (2015) Russell, Joseph; Hsieh, Adam H; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Degenerative disc disease is commonly linked with low back pain, a major musculoskeletal disorder contributing to an annual socioeconomic impact of over $100 billion. The intervertebral disc (IVD) plays a critical role in spinal load bearing and many of the mechanisms of its degeneration are still unknown. This study focused on eliciting gene expression changes of the Nucleus Pulposus (NP), the inner region of the IVD critical to load support using an in vivo rat model. First, pneumatic artificial muscles (PAMs) were calibrated and integrated into a small loading device as an actuation mechanism. Next, various load histories were then applied on IVDs and gene expression was determined by qRT-PCR. Results show that discs with increased intradiscal pressure led increased expression of genes common to the NP. This study contributes to the better understanding of how load history alters IVD health and validates a device for future long term studies.