Probing cellular mechanobiology in three-dimensional culture with collagen-agarose matrices.
نویسندگان
چکیده
The study of how cell behavior is controlled by the biophysical properties of the extracellular matrix (ECM) is limited in part by the lack of three-dimensional (3D) scaffolds that combine the biofunctionality of native ECM proteins with the tunability of synthetic materials. Here, we introduce a biomaterial platform in which the biophysical properties of collagen I are progressively altered by adding agarose. We find that agarose increases the elasticity of 3D collagen ECMs over two orders of magnitude with modest effect on collagen fiber organization. Surprisingly, increasing the agarose content slows and eventually stops invasion of glioma cells in a 3D spheroid model. Electron microscopy reveals that agarose forms a dense meshwork between the collagen fibers, which we postulate slows invasion by structurally coupling and reinforcing the collagen fibers and introducing steric barriers to motility. This is supported by time lapse imaging of individual glioma cells and multicellular spheroids, which shows that addition of agarose promotes amoeboid motility and restricts cell-mediated remodeling of individual collagen fibers. Our results are consistent with a model in which agarose shifts ECM dissipation of cell-induced stresses from non-affine deformation of individual collagen fibers to bulk-affine deformation of a continuum network.
منابع مشابه
3D collagen cultures under well-defined dynamic strain: a novel strain device with a porous elastomeric support.
The field of mechanobiology has grown tremendously in the past few decades, and it is now well accepted that dynamic stresses and strains can impact cell and tissue organization, cell-cell and cell-matrix communication, matrix remodeling, cell proliferation and apoptosis, cell migration, and many other cell behaviors in both physiological and pathophysiological situations. Natural reconstituted...
متن کاملEvaluation of Human Breast Adenocarcinoma (MCF-7) Cells Proliferation in Co-Culture with Human Adipocytes in Three Dimensional Collagen Gel Matrix: Norepinephrine as a Lipolytic Factor
Background: Norepinephrine plays a trophic role in the control of cell replication and differentiation in target cells that express adrenergic receptors. Methods: In this study, we have tested the influence of infraphysiological, physiological and supraphysiological concentrations (0.0001 nM, 1 nM, 10000 nM) of human norepinephrine on the proliferation of breast cancer cells (human breast adeno...
متن کاملTechniques for assessing 3-D cell-matrix mechanical interactions in vitro and in vivo.
Cellular interactions with extracellular matrices (ECM) through the application of mechanical forces mediate numerous biological processes including developmental morphogenesis, wound healing and cancer metastasis. They also play a key role in the cellular repopulation and/or remodeling of engineered tissues and organs. While 2-D studies can provide important insights into many aspects of cellu...
متن کاملPreparation of Porous Collagen Matrices and Their Interaction with Different Cell Types
The aim of our research was to obtain porous matrices from collagen and collagen-hyaluronic acid and to investigate their effect on two types of human cells: fibroblasts and osteoblasts. In order to fabricate the collagenous matrices, type I collagen solution and a mixture of type I collagen and hyaluronic acid solutions, in a weight ratio of 5:1 were conditioned as sponges by freeze-drying. ES...
متن کاملShear-wave elasticity measurements of three-dimensional cell cultures for mechanobiology
Studying mechanobiology in three-dimensional (3D) cell cultures better recapitulates cell behaviors in response to various types of mechanical stimuli in vivo Stiffening of the extracellular matrix resulting from cell remodeling potentiates many pathological conditions, including advanced cancers. However, an effective tool for measuring the spatiotemporal changes in elastic properties of such ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Biomaterials
دوره 31 7 شماره
صفحات -
تاریخ انتشار 2010