期刊
BIOMATERIALS
卷 32, 期 24, 页码 5633-5642出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.04.045
关键词
Brain; Cell adhesion; Hydrogel; ECM (extracellular matrix); Mechanical properties; Elasticity
资金
- UC Berkeley Graduate Division, National Science Foundation
- National Defense Science
- UC Berkeley
- UC Cancer Research Coordinating Committee
- NSF [CMMI 0727420]
- NIH (Physical Sciences Oncology Center) [1U54CA143836]
- NIH Roadmap for Medical Research [1DP2OD004213]
- MEST, South Korea
Cells are strongly influenced by the local structure and mechanics of the extracellular matrix (ECM). We recently showed that adding agarose to soft collagen ECMs can mechanically stiffen these hydrogels by two orders of magnitude while limiting 3D cell motility, which we speculated might derive from agarose-mediated inhibition of collagen fiber deformation and remodeling. Here, we directly address this hypothesis by investigating the effects of agarose on cell collagen interactions at the microscale. Addition of agarose progressively restricts cell spreading, reduces stress fiber and focal adhesion assembly, and inhibits macroscopic gel compaction. While time-of-flight secondary ion mass spectrometry and scanning electron microscopy fail to reveal agarose-induced alterations in collagen ligand presentation, the latter modality shows that agarose strongly impairs cell-directed assembly of large collagen bundles. Agarose-mediated inhibition of cell spreading and cytoarchitecture can be rescued by B-agarase digestion or by covalently crosslinking the matrix with glutaraldehyde. Based on these results, we argue that cell spreading and motility on collagen requires local matrix stiffening, which can be achieved via cell-mediated fiber remodeling or by chemically crosslinking the fibers. These findings provide new mechanistic insights into the regulatory function of agarose and bear general implications for cell adhesion and motility in fibrous ECMs. (C) 2011 Elsevier Ltd. All rights reserved.
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