Nuclear stiffening and chromatin softening with progerin expression leads to an attenuated nuclear response to force.

Progerin is a mutant form of the nucleoskeletal protein lamin A, and its expression results in the rare premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS). Patients with HGPS demonstrate several characteristic signs of aging including cardiovascular and skeletal dysfunction. Cells from HGPS patients show several nuclear abnormalities including aberrant morphology, nuclear stiffening and loss of epigenetic modifications including heterochromatin territories.

Probing the biophysical properties of primary breast tumor-derived fibroblasts.

As cancer progresses, cells must adapt to a new and stiffer environment, which can ultimately alter how normal cells within the tumor behave. In turn, these cells are known to further aid tumor progression. Therefore, there is potentially a unique avenue to better understand metastatic potential through single-cell biophysical assays performed on patient-derived cells.

Physical biology in cancer. 5. The rocky road of metastasis: the role of cytoskeletal mechanics in cell migratory response to 3D matrix topography.

The tumor microenvironment is a milieu of heterogeneous architectural features that affect tumor growth and metastatic invasion. Pore size, density, stiffness, and fiber architecture change dramatically from location to location throughout the tumor matrix. While many studies have addressed the effects of two-dimensional extracellular matrix structure and composition on cell migration, less is known about how cancer cells navigate complex, heterogeneous three-dimensional (3D) microenvironments.

Force-induced changes in subnuclear movement and rheology.

Extracellular mechanical forces result in changes in gene expression, but it is unclear how cells are able to permanently adapt to new mechanical environments because chemical signaling pathways are short-lived. We visualize force-induced changes in nuclear rheology to examine short- and long-time genome organization and movements. Punctate labels in the nuclear interior of HeLa, human umbilical vein endothelial, and osteosarcoma (Saos-2) cells allow tracking of nuclear movements in cells under varying levels of shear and compressive force.