Legant, WR and Pathak, A and Yang, MT and Deshpande, VS and McMeeking, RM and Chen, CS (2009) Microfabricated tissue gauges to measure and manipulate forces from 3D microtissues. Proceedings of the National Academy of Sciences of the United States of America, 106. pp. 10097-10102. ISSN 0027-8424Full text not available from this repository.
Physical forces generated by cells drive morphologic changes during development and can feedback to regulate cellular phenotypes. Because these phenomena typically occur within a 3-dimensional (3D) matrix in vivo, we used microelectromechanical systems (MEMS) technology to generate arrays of microtissues consisting of cells encapsulated within 3D micropatterned matrices. Microcantilevers were used to simultaneously constrain the remodeling of a collagen gel and to report forces generated during this process. By concurrently measuring forces and observing matrix remodeling at cellular length scales, we report an initial correlation and later decoupling between cellular contractile forces and changes in tissue morphology. Independently varying the mechanical stiffness of the cantilevers and collagen matrix revealed that cellular forces increased with boundary or matrix rigidity whereas levels of cytoskeletal and extracellular matrix (ECM) proteins correlated with levels of mechanical stress. By mapping these relationships between cellular and matrix mechanics, cellular forces, and protein expression onto a bio-chemo-mechanical model of microtissue contractility, we demonstrate how intratissue gradients of mechanical stress can emerge from collective cellular contractility and finally, how such gradients can be used to engineer protein composition and organization within a 3D tissue. Together, these findings highlight a complex and dynamic relationship between cellular forces, ECM remodeling, and cellular phenotype and describe a system to study and apply this relationship within engineered 3D microtissues.
|Uncontrolled Keywords:||Biomechanics Cell mechanics Collagen Morphogenesis PDMS|
|Divisions:||Div C > Materials Engineering|
|Depositing User:||Cron job|
|Date Deposited:||04 Feb 2015 22:44|
|Last Modified:||02 Mar 2015 01:25|