The sequencing of the human genome has provided a wealth of scientific information, but this information is limited by the poor understanding of the mechanisms which control gene expression. We examine changes in nuclear mechanics in cells which are differentiating, de-differentiating via cancer progression and aging. We perform static mechanical measurements of bone marrow derived stem cells, metastatic cancer cells and cells from patients with premature aging. We are able to quantify mechanics and determine contributions of subcellular features, including the nucleus. ‘Undecided’ cells, including stem cells and cancer cells, have much softer nuclei whereas aged cells have stiffer nuclei. We also examine the role that force plays in altering nuclear mechanics and gene expression. Mechanical force and proper cellular response is important during development and for proper homeostatic maintenance of cells and tissues. The genome within the nucleus is a complex, self-assembled structure which has unique mechanical properties capable of responding proportionally to both the magnitude and duration of applied forces. We track subnuclear reorganization in cells with applied forces using particle tracking. We find distinct temporal regimes of subnuclear movements as nuclei adapt to shear stress by stiffening. We have found that native, endogenous structures appear to be in a mechanical homeostasis such that they can sense and adapt optimally to force. Together, it appears that the mechanics and mechanical response of the nuclei in cells is important for proper cell function.  

The sequencing of the human genome has provided a wealth of scientific information, but this information is limited by the poor understanding of the mechanisms which control gene expression. We examine changes in nuclear mechanics in cells which are differentiating, de-differentiating via cancer progression and aging. We perform static mechanical measurements of bone marrow derived stem cells, metastatic cancer cells and cells from patients with premature aging. We are able to quantify mechanics and determine contributions of subcellular features, including the nucleus. ‘Undecided’ cells, including stem cells and cancer cells, have much softer nuclei whereas aged cells have stiffer nuclei. We also examine the role that force plays in altering nuclear mechanics and gene expression. Mechanical force and proper cellular response is important during development and for proper homeostatic maintenance of cells and tissues. The genome within the nucleus is a complex, self-assembled structure which has unique mechanical properties capable of responding proportionally to both the magnitude and duration of applied forces. We track subnuclear reorganization in cells with applied forces using particle tracking. We find distinct temporal regimes of subnuclear movements as nuclei adapt to shear stress by stiffening. We have found that native, endogenous structures appear to be in a mechanical homeostasis such that they can sense and adapt optimally to force. Together, it appears that the mechanics and mechanical response of the nuclei in cells is important for proper cell function.  

Associate Professor Carnegie Mellon University

Associate Professor Carnegie Mellon University

Department of Biomedical Engineering, Department of Chemical Engineering

Department of Biomedical Engineering, Department of Chemical Engineering