@article {236, title = {Deconstructing Signaling in 3 Dimensions.}, journal = {Biochemistry}, year = {2014}, month = {2014 Mar 20}, abstract = {

Cells in vivo exist within the context of a multicellular tissue, where their behavior is governed by homo- and heterotypic cell-cell interactions, the material properties of the extracellular matrix, and the distribution and accessibility of various soluble and physical factors. Yet, most of the methods currently used to study and manipulate cellular behavior in vitro sacrifice physiological relevance for experimental expediency. The fallacy of such approaches to biological investigation has been highlighted by the recent development and application of three dimensional culture models to cell biology, which have revealed striking phenotypic differences in cell survival, migration, and differentiation in otherwise seemingly identical cells simply by varying culture conditions. These perplexing findings beg the question: what constitutes a three dimensional culture and why do cells behave so differently in a two versus a three dimensional culture format? In the following review, we dissect the fundamental differences between two and three dimensional culture conditions. We begin by establishing a basic definition of what \"three dimensions\" means at different biological scales and discuss how dimensionality influences cell signaling across different length scales. We identify which three dimensional features most potently influence intracellular signaling and distinguish between conserved biological principles that are maintained across culture conditions and cellular behaviors that are sensitive to microenvironmental context. Finally, we highlight state of the art molecular tools amenable to the study of signaling in three dimensions under conditions that facilitate deconstructing cell signaling in a more physiologically relevant manner.

}, issn = {1520-4995}, doi = {10.1021/bi401710d}, author = {Rubashkin, Matthew G and Ou, Guanqing and Weaver, Valerie M} } @article {341, title = {Dynamic interplay between the collagen scaffold and tumor evolution.}, journal = {Curr Opin Cell Biol}, volume = {22}, year = {2010}, month = {2010 Oct}, pages = {697-706}, abstract = {

The extracellular matrix (ECM) is a key regulator of cell and tissue function. Traditionally, the ECM has been thought of primarily as a physical scaffold that binds cells and tissues together. However, the ECM also elicits biochemical and biophysical signaling. Controlled proteolysis and remodeling of the ECM network regulate tissue tension, generate pathways for migration, and release ECM protein fragments to direct normal developmental processes such as branching morphogenesis. Collagens are major components of the ECM of which basement membrane type IV and interstitial matrix type I are the most prevalent. Here we discuss how abnormal expression, proteolysis and structure of these collagens influence cellular functions to elicit multiple effects on tumors, including proliferation, initiation, invasion, metastasis, and therapy response.

}, keywords = {Cell Movement, Collagen, Humans, Neoplasms, Tissue Scaffolds}, issn = {1879-0410}, doi = {10.1016/j.ceb.2010.08.015}, author = {Egeblad, Mikala and Rasch, Morten G and Weaver, Valerie M} } @article {511, title = {Death in the third dimension: apoptosis regulation and tissue architecture.}, journal = {Curr Opin Genet Dev}, volume = {14}, year = {2004}, month = {2004 Feb}, pages = {71-80}, abstract = {

Tissue development, homeostasis and tumor pathogenesis all depend upon a complex dialogue between multiple cell types operating within a dynamic three-dimensional (3D) tissue extracellular matrix microenvironment. A major issue is whether the spatial organization of a cell within this 3D tissue microenvironment could modulate cell responsiveness to regulate cell fate decisions such as survival, and if so how. Classic developmental model systems and transgenic animals are instructive but pose special challenges for investigators conducting signaling studies and biochemical assays in tissues. As an alternative, 3D culture model systems exist in which cell-adhesion dependent tissue architecture, heterotypic cell-cell interactions and tissue differentiation can be recapitulated with good fidelity. 3D cell culture models are slowly revealing how tissue architecture can dramatically influence how a cell responds to exogenous stimuli to modify its apoptotic behavior and hence should prove instrumental for identifying novel cell death pathways.

}, keywords = {Apoptosis, Cell Adhesion, Cell Culture Techniques, Extracellular Matrix, Gene Expression Regulation, Homeostasis, Models, Biological}, issn = {0959-437X}, doi = {10.1016/j.gde.2003.12.005}, author = {Zahir, Nastaran and Weaver, Valerie M} }