Dataset Information

Mapping of mechanical strains and stresses around quiescent engineered three-dimensional epithelial tissues.

ABSTRACT: Understanding how physical signals guide biological processes requires qualitative and quantitative knowledge of the mechanical forces generated and sensed by cells in a physiologically realistic three-dimensional (3D) context. Here, we used computational modeling and engineered epithelial tissues of precise geometry to define the experimental parameters that are required to measure directly the mechanical stress profile of 3D tissues embedded within native type I collagen. We found that to calculate the stresses accurately in these settings, we had to account for mechanical heterogeneities within the matrix, which we visualized and quantified using confocal reflectance and atomic force microscopy. Using this technique, we were able to obtain traction forces at the epithelium-matrix interface, and to resolve and quantify patterns of mechanical stress throughout the surrounding matrix. We discovered that whereas single cells generate tension by contracting and pulling on the matrix, the contraction of multicellular tissues can also push against the matrix, causing emergent compression. Furthermore, tissue geometry defines the spatial distribution of mechanical stress across the epithelium, which communicates mechanically over distances spanning hundreds of micrometers. Spatially resolved mechanical maps can provide insight into the types and magnitudes of physical parameters that are sensed and interpreted by multicellular tissues during normal and pathological processes.

SUBMITTER: Gjorevski N

PROVIDER: S-EPMC3388222 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Mapping of mechanical strains and stresses around quiescent engineered three-dimensional epithelial tissues.

Gjorevski Nikolce N Nelson Celeste M CM

Biophysical journal 20120701 1

Understanding how physical signals guide biological processes requires qualitative and quantitative knowledge of the mechanical forces generated and sensed by cells in a physiologically realistic three-dimensional (3D) context. Here, we used computational modeling and engineered epithelial tissues of precise geometry to define the experimental parameters that are required to measure directly the mechanical stress profile of 3D tissues embedded within native type I collagen. We found that to calc ...[more]

PMID: 22828342

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Project description:Cardiovascular tissue engineering is a promising approach to develop grafts that, in contrast to current replacement grafts, have the capacity to grow and remodel like native tissues. This approach largely depends on cell-driven tissue growth and remodeling, which are highly complex processes that are difficult to control inside the scaffolds used for tissue engineering. For several tissue engineering approaches, adverse tissue growth and remodeling outcomes were reported, such as aneurysm formation in vascular grafts, and leaflet retraction in heart valve grafts. It is increasingly recognized that the outcome of tissue growth and remodeling, either physiological or pathological, depends at least partly on the establishment of a homeostatic mechanical state, where one or more mechanical quantities in a tissue are maintained in equilibrium. To design long-term functioning tissue engineering strategies, understanding how scaffold parameters such as geometry affect the mechanical state of a construct, and how this state guides tissue growth and remodeling, is therefore crucial. Here, we studied how anisotropic versus isotropic mechanical loading-as imposed by initial scaffold geometry-influences tissue growth, remodeling, and the evolution of the mechanical state and geometry of tissue-engineered cardiovascular constructs in vitro. Using a custom-built bioreactor platform and nondestructive mechanical testing, we monitored the mechanical and geometric changes of elliptical and circular, vascular cell-seeded, polycaprolactone-bisurea scaffolds during 14 days of dynamic loading. The elliptical and circular scaffold geometries were designed using finite element analysis, to induce anisotropic and isotropic dynamic loading, respectively, with similar maximum stretch when cultured in the bioreactor platform. We found that the initial scaffold geometry-induced (an)isotropic loading of the engineered constructs differentially dictated the evolution of their mechanical state and geometry over time, as well as their final structural organization. These findings demonstrate that controlling the initial mechanical state of tissue-engineered constructs via scaffold geometry can be used to influence tissue growth and remodeling and determine tissue outcomes.

Dataset Information

Mapping of mechanical strains and stresses around quiescent engineered three-dimensional epithelial tissues.

Publications

Mapping of mechanical strains and stresses around quiescent engineered three-dimensional epithelial tissues.

Similar Datasets

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