@article {231, title = {Scanning angle interference microscopy reveals cell dynamics at the nanoscale.}, journal = {Nat Methods}, volume = {9}, year = {2012}, month = {2012 Aug}, pages = {825-7}, abstract = {

Emerging questions in cell biology necessitate nanoscale imaging in live cells. Here we present scanning angle interference microscopy, which is capable of localizing fluorescent objects with nanoscale precision along the optical axis in motile cellular structures. We use this approach to resolve nanotopographical features of the cell membrane and cytoskeleton as well as the temporal evolution, three-dimensional architecture and nanoscale dynamics of focal adhesion complexes.

}, keywords = {Cell Membrane, Cells, Cultured, Cytoskeleton, Epithelial Cells, Fibronectins, Focal Adhesions, Humans, Microscopy, Interference, Nanotechnology}, issn = {1548-7105}, doi = {10.1038/nmeth.2077}, author = {Paszek, Matthew J and DuFort, Christopher C and Rubashkin, Matthew G and Davidson, Michael W and Thorn, Kurt S and Liphardt, Jan T and Weaver, Valerie M} } @article {386, title = {A tense situation: forcing tumour progression.}, journal = {Nat Rev Cancer}, volume = {9}, year = {2009}, month = {2009 Feb}, pages = {108-22}, abstract = {

Cells within tissues are continuously exposed to physical forces including hydrostatic pressure, shear stress, and compression and tension forces. Cells dynamically adapt to force by modifying their behaviour and remodelling their microenvironment. They also sense these forces through mechanoreceptors and respond by exerting reciprocal actomyosin- and cytoskeletal-dependent cell-generated force by a process termed \&$\#$39;mechanoreciprocity\&$\#$39;. Loss of mechanoreciprocity has been shown to promote the progression of disease, including cancer. Moreover, the mechanical properties of a tissue contribute to disease progression, compromise treatment and might also alter cancer risk. Thus, the changing force that cells experience needs to be considered when trying to understand the complex nature of tumorigenesis.

}, keywords = {Animals, Cell Transformation, Neoplastic, Cytoskeleton, Disease Progression, Gene Expression, Humans, Mechanotransduction, Cellular, Neoplasms, Neoplastic Processes, Stress, Mechanical}, issn = {1474-1768}, doi = {10.1038/nrc2544}, author = {Butcher, Darci T and Alliston, Tamara and Weaver, Valerie M} } @article {421, title = {Tensional homeostasis and the malignant phenotype.}, journal = {Cancer Cell}, volume = {8}, year = {2005}, month = {2005 Sep}, pages = {241-54}, abstract = {

Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation. Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ERK activation and increase ROCK-generated contractility and focal adhesions. Contractile, EGF-transformed epithelia with elevated ERK and Rho activity could be phenotypically reverted to tissues lacking focal adhesions if Rho-generated contractility or ERK activity was decreased. Thus, ERK and Rho constitute part of an integrated mechanoregulatory circuit linking matrix stiffness to cytoskeletal tension through integrins to regulate tissue phenotype.

}, keywords = {3T3 Cells, Animals, Cell Line, Tumor, Cell Shape, Cytoskeleton, Homeostasis, Mice, Neoplasms, Phenotype, Stress, Mechanical, Stromal Cells}, issn = {1535-6108}, doi = {10.1016/j.ccr.2005.08.010}, author = {Paszek, Matthew J and Zahir, Nastaran and Johnson, Kandice R and Lakins, Johnathon N and Rozenberg, Gabriela I and Gefen, Amit and Reinhart-King, Cynthia A and Margulies, Susan S and Dembo, Micah and Boettiger, David and Hammer, Daniel A and Weaver, Valerie M} }