@article {6955,
	title = {Microfabrication of a platform to measure and manipulate the mechanics of engineered microtissues.},
	journal = {Methods in Cell Biology},
	volume = {121},
	year = {2014},
	month = {2014},
	pages = {191-211},
	abstract = {<p>Engineered tissues can be used to understand fundamental features of biology, develop organotypic in vitro model systems, and as engineered tissue constructs for replacing damaged tissue in vivo. However, a key limitation is an inability to test the wide range of parameters that might impact the engineered tissue in a high-throughput manner and in an environment that mimics the three-dimensional (3D) native architecture. We developed a microfabricated platform to generate arrays of microtissues embedded within 3D micropatterned matrices. Microcantilevers simultaneously constrain microtissue formation and report forces generated by the microtissues in real time, opening the possibility to use high-throughput, low-volume screening for studies on engineered tissues. Thanks to the micrometer scale of the microtissues, this platform is also suitable for high-throughput monitoring of drug-induced effect on architecture and contractility in engineered tissues. Moreover, independent variations of the mechanical stiffness of the cantilevers and collagen matrix allow the measurement and manipulation of the mechanics of the microtissues. Thus, our approach will likely provide valuable opportunities to elucidate how biomechanical, electrical, biochemical, and genetic/epigenetic cues modulate the formation and maturation of 3D engineered tissues. In this chapter, we describe the microfabrication, preparation, and experimental use of such microfabricated tissue gauges.</p>
},
	issn = {0091-679X},
	doi = {10.1016/B978-0-12-800281-0.00013-0},
	author = {Ramade, Alexandre and Legant, Wesley R and Picart, Catherine and Chen, Christopher S and Boudou, Thomas}
}
@article {6292,
	title = {Multidimensional traction force microscopy reveals out-of-plane rotational moments about focal adhesions.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {110},
	year = {2013},
	month = {2013 Jan 15},
	pages = {881-6},
	abstract = {<p>Recent methods have revealed that cells on planar substrates exert both shear (in-plane) and normal (out-of-plane) tractions against the extracellular matrix (ECM). However, the location and origin of the normal tractions with respect to the adhesive and cytoskeletal elements of cells have not been elucidated. We developed a high-spatiotemporal-resolution, multidimensional (2.5D) traction force microscopy to measure and model the full 3D nature of cellular forces on planar 2D surfaces. We show that shear tractions are centered under elongated focal adhesions whereas upward and downward normal tractions are detected on distal (toward the cell edge) and proximal (toward the cell body) ends of adhesions, respectively. Together, these forces produce significant rotational moments about focal adhesions in both protruding and retracting peripheral regions. Temporal 2.5D traction force microscopy analysis of migrating and spreading cells shows that these rotational moments are highly dynamic, propagating outward with the leading edge of the cell. Finally, we developed a finite element model to examine how rotational moments could be generated about focal adhesions in a thin lamella. Our model suggests that rotational moments can be generated largely via shear lag transfer to the underlying ECM from actomyosin contractility applied at the intracellular surface of a rigid adhesion of finite thickness. Together, these data demonstrate and probe the origin of a previously unappreciated multidimensional stress profile associated with adhesions and highlight the importance of new approaches to characterize cellular forces.</p>
},
	keywords = {Animals, Biological, Biophysical Phenomena, Cellular, Fibroblasts, Finite Element Analysis, Fluorescence, Focal Adhesions, Green Fluorescent Proteins, Mechanotransduction, Mice, Microscopy, Models, Recombinant Proteins, Rotation},
	issn = {1091-6490},
	doi = {10.1073/pnas.1207997110},
	author = {Legant, Wesley R and Choi, Colin K and Miller, Jordan S and Shao, Lin and Gao, Liang and Betzig, Eric and Chen, Christopher S}
}
