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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Guo, Wei-hui Wang, Yu-li Wong, Stephanie |
| Description | Author Affiliation: Wong S ( Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219.); Guo WH ( Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219.); Wang YL ( Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219 yuliwang@andrew.cmu.edu.); |
| Abstract | Rigidity sensing and durotaxis are thought to be important elements in wound healing, tissue formation, and cancer treatment. It has been challenging, however, to study the underlying mechanism due to difficulties in capturing cells during the transient response to a rigidity interface. We have addressed this problem by developing a model experimental system that confines cells to a micropatterned area with a rigidity border. The system consists of a rigid domain of one large adhesive island, adjacent to a soft domain of small adhesive islands grafted on a nonadhesive soft gel. This configuration allowed us to test rigidity sensing away from the cell body during probing and spreading. NIH 3T3 cells responded to the micropatterned rigidity border similarly to cells at a conventional rigidity border, by showing a strong preference for staying on the rigid side. Furthermore, cells used filopodia extensions to probe substrate rigidity at a distance in front of the leading edge and regulated their responses based on the strain of the intervening substrate. Soft substrates inhibited focal adhesion maturation and promoted cell retraction, whereas rigid substrates allowed stable adhesions and cell spreading. Myosin II was required for not only the generation of probing forces but also the retraction in response to soft substrates. We suggest that a myosin II-driven, filopodia-based probing mechanism ahead of the leading edge allows cells to migrate efficiently, by sensing physical characteristics before moving over a substrate to avoid backtracking. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 48 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Movement Physiology Fibroblasts Focal Adhesions Pseudopodia Animals Cell Adhesion Drug Effects Cell Physiological Phenomena Cellular Microenvironment Cytology Metabolism Heterocyclic Compounds With 4 Or More Rings Pharmacology Hydrogels Mice Microscopy, Electron, Scanning Microscopy, Fluorescence Microscopy, Phase-Contrast Models, Biological Myosin Type II Antagonists & Inhibitors NIH 3T3 Cells Ultrastructure Surface Properties Time-Lapse Imaging Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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