@article {301,
	title = {In situ force mapping of mammary gland transformation.},
	journal = {Integr Biol (Camb)},
	volume = {3},
	year = {2011},
	month = {2011 Sep},
	pages = {910-21},
	abstract = {<p>Tumor progression is characterized by an incremental stiffening of the tissue. The importance of tissue rigidity to cancer is appreciated, yet the contribution of specific tissue elements to tumor stiffening and their physiological significance remains unclear. We performed high-resolution atomic force microscopy indentation in live and snap-frozen fluorescently labeled mammary tissues to explore the origin of the tissue stiffening associated with mammary tumor development in PyMT mice. The tumor epithelium, the tumor-associated vasculature and the extracellular matrix all contributed to mammary gland stiffening as it transitioned from normal to invasive carcinoma. Consistent with the concept that extracellular matrix stiffness modifies cell tension, we found that isolated transformed mammary epithelial cells were intrinsically stiffer than their normal counterparts but that the malignant epithelium in situ was far stiffer than isolated breast tumor cells. Moreover, using an in situ vitrification approach, we determined that the extracellular matrix adjacent to the epithelium progressively stiffened as tissue evolved from normal through benign to an invasive state. Importantly, we also noted that there was significant mechanical heterogeneity within the transformed tissue both in the epithelium and the tumor-associated neovasculature. The vascular bed within the tumor core was substantially stiffer than the large patent vessels at the invasive front that are surrounded by the stiffest extracellular matrix. These findings clarify the contribution of individual mammary gland tissue elements to the altered biomechanical landscape of cancerous tissues and emphasize the importance of studying cancer cell evolution under conditions that preserve native interactions.</p>
},
	keywords = {Animals, Bioengineering, Biomechanical Phenomena, Biophysical Phenomena, Cell Transformation, Neoplastic, Extracellular Matrix, Female, Mammary Glands, Animal, Mammary Neoplasms, Experimental, Mammary Tumor Virus, Mouse, Mice, Mice, Transgenic, Microscopy, Atomic Force, Neoplasm Invasiveness, Retroviridae Infections, Tensile Strength, Tumor Virus Infections, Vitrification},
	issn = {1757-9708},
	doi = {10.1039/c1ib00043h},
	author = {Lopez, Jose I and Kang, Inkyung and You, Weon-Kyoo and McDonald, Donald M and Weaver, Valerie M}
}
@article {361,
	title = {Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate.},
	journal = {PLoS Comput Biol},
	volume = {5},
	year = {2009},
	month = {2009 Dec},
	pages = {e1000604},
	abstract = {<p>Integrins have emerged as key sensory molecules that translate chemical and physical cues from the extracellular matrix (ECM) into biochemical signals that regulate cell behavior. Integrins function by clustering into adhesion plaques, but the molecular mechanisms that drive integrin clustering in response to interaction with the ECM remain unclear. To explore how deformations in the cell-ECM interface influence integrin clustering, we developed a spatial-temporal simulation that integrates the micro-mechanics of the cell, glycocalyx, and ECM with a simple chemical model of integrin activation and ligand interaction. Due to mechanical coupling, we find that integrin-ligand interactions are highly cooperative, and this cooperativity is sufficient to drive integrin clustering even in the absence of cytoskeletal crosslinking or homotypic integrin-integrin interactions. The glycocalyx largely mediates this cooperativity and hence may be a key regulator of integrin function. Remarkably, integrin clustering in the model is naturally responsive to the chemical and physical properties of the ECM, including ligand density, matrix rigidity, and the chemical affinity of ligand for receptor. Consistent with experimental observations, we find that integrin clustering is robust on rigid substrates with high ligand density, but is impaired on substrates that are highly compliant or have low ligand density. We thus demonstrate how integrins themselves could function as sensory molecules that begin sensing matrix properties even before large multi-molecular adhesion complexes are assembled.</p>
},
	keywords = {Algorithms, Computer Simulation, Extracellular Matrix, Glycocalyx, Integrins, Ligands, Protein Binding, Stress, Physiological, Substrate Specificity},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.1000604},
	author = {Paszek, Matthew J and Boettiger, David and Weaver, Valerie M and Hammer, Daniel A}
}
