Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels
The mechanical environment plays an important role in cell signaling and tissue homeostasis. Unraveling connections between externally applied loads and the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for exami...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2009-10, Vol.106 (42), p.17675-17680 |
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creator | Sander, Edward A Stylianopoulos, Triantafyllos Tranquillo, Robert T Barocas, Victor H |
description | The mechanical environment plays an important role in cell signaling and tissue homeostasis. Unraveling connections between externally applied loads and the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for examining the fine details of tissue behavior, but they require validation at multiple scales. In this study, we developed a multiscale model that captured the anisotropy and heterogeneity of a cell-compacted collagen gel subjected to an off-axis hold mechanical test and subsequently to biaxial extension. In both the model and experiments, the ECM reorganized in a nonaffine and heterogeneous manner that depended on multiscale interactions between the fiber networks. Simulations predicted that tensile and compressive fiber forces were produced to accommodate macroscopic displacements. Fiber forces in the simulation ranged from -11.3 to 437.7 nN, with a significant fraction of fibers under compression (12.1% during off-axis stretch). The heterogeneous network restructuring predicted by the model serves as an example of how multiscale modeling techniques provide a theoretical framework for understanding relationships between ECM structure and tissue-level mechanical properties and how microscopic fiber rearrangements could lead to mechanotransductive cell signaling. |
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Unraveling connections between externally applied loads and the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for examining the fine details of tissue behavior, but they require validation at multiple scales. In this study, we developed a multiscale model that captured the anisotropy and heterogeneity of a cell-compacted collagen gel subjected to an off-axis hold mechanical test and subsequently to biaxial extension. In both the model and experiments, the ECM reorganized in a nonaffine and heterogeneous manner that depended on multiscale interactions between the fiber networks. Simulations predicted that tensile and compressive fiber forces were produced to accommodate macroscopic displacements. Fiber forces in the simulation ranged from -11.3 to 437.7 nN, with a significant fraction of fibers under compression (12.1% during off-axis stretch). The heterogeneous network restructuring predicted by the model serves as an example of how multiscale modeling techniques provide a theoretical framework for understanding relationships between ECM structure and tissue-level mechanical properties and how microscopic fiber rearrangements could lead to mechanotransductive cell signaling.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0903716106</identifier><identifier>PMID: 19805118</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Anisotropy ; Biochemistry ; Biological Sciences ; Biomechanical Phenomena ; Cells ; Collagen Type I - chemistry ; Collagen Type I - physiology ; Collagens ; Compressive Strength - physiology ; Connective tissues ; Extracellular Matrix - chemistry ; Extracellular Matrix - physiology ; Fibroblasts ; Fibroblasts - physiology ; Fracture mechanics ; Gels ; Homeostasis - physiology ; Humans ; In Vitro Techniques ; Mechanical engineering ; Mechanics ; Mechanotransduction, Cellular - physiology ; Modeling ; Models, Biological ; Models, Molecular ; Multiprotein Complexes ; Multiscale modeling ; Parametric models ; Physical Sciences ; Proteins ; Signal Transduction - physiology ; Tensile Strength - physiology ; Tissues</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2009-10, Vol.106 (42), p.17675-17680</ispartof><rights>Copyright National Academy of Sciences Oct 20, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c590t-f69a38ef50e316338ab1894c6cb0fc0728988ad89c2106c89d056c172e33343e3</citedby><cites>FETCH-LOGICAL-c590t-f69a38ef50e316338ab1894c6cb0fc0728988ad89c2106c89d056c172e33343e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/106/42.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25592889$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25592889$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27926,27927,53793,53795,58019,58252</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19805118$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sander, Edward A</creatorcontrib><creatorcontrib>Stylianopoulos, Triantafyllos</creatorcontrib><creatorcontrib>Tranquillo, Robert T</creatorcontrib><creatorcontrib>Barocas, Victor H</creatorcontrib><title>Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The mechanical environment plays an important role in cell signaling and tissue homeostasis. Unraveling connections between externally applied loads and the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for examining the fine details of tissue behavior, but they require validation at multiple scales. In this study, we developed a multiscale model that captured the anisotropy and heterogeneity of a cell-compacted collagen gel subjected to an off-axis hold mechanical test and subsequently to biaxial extension. In both the model and experiments, the ECM reorganized in a nonaffine and heterogeneous manner that depended on multiscale interactions between the fiber networks. Simulations predicted that tensile and compressive fiber forces were produced to accommodate macroscopic displacements. Fiber forces in the simulation ranged from -11.3 to 437.7 nN, with a significant fraction of fibers under compression (12.1% during off-axis stretch). The heterogeneous network restructuring predicted by the model serves as an example of how multiscale modeling techniques provide a theoretical framework for understanding relationships between ECM structure and tissue-level mechanical properties and how microscopic fiber rearrangements could lead to mechanotransductive cell signaling.</description><subject>Anisotropy</subject><subject>Biochemistry</subject><subject>Biological Sciences</subject><subject>Biomechanical Phenomena</subject><subject>Cells</subject><subject>Collagen Type I - chemistry</subject><subject>Collagen Type I - physiology</subject><subject>Collagens</subject><subject>Compressive Strength - physiology</subject><subject>Connective tissues</subject><subject>Extracellular Matrix - chemistry</subject><subject>Extracellular Matrix - physiology</subject><subject>Fibroblasts</subject><subject>Fibroblasts - physiology</subject><subject>Fracture mechanics</subject><subject>Gels</subject><subject>Homeostasis - physiology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Mechanical engineering</subject><subject>Mechanics</subject><subject>Mechanotransduction, Cellular - physiology</subject><subject>Modeling</subject><subject>Models, Biological</subject><subject>Models, Molecular</subject><subject>Multiprotein Complexes</subject><subject>Multiscale modeling</subject><subject>Parametric models</subject><subject>Physical Sciences</subject><subject>Proteins</subject><subject>Signal Transduction - physiology</subject><subject>Tensile Strength - physiology</subject><subject>Tissues</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhSMEoqWwZgVYbBCLtNdx4tibSqjiUakSC-ja8jg3qQfHHmynPH4AvxuPZtQBNqws-3w-9rmnqp5SOKXQs7ON1-kUJLCecgr8XnVMQdKatxLuV8cATV-LtmmPqkcprQFAdgIeVkdUCugoFcfVr8tZT1ivdMKBzIvLNhntkMxhQGf9RDYRB2tyIkVJC9YOb9ER7QfiMX8L8cv-ZLQrjCRiiJP29qfONnhiPUk5YjY3xd2gc7UJ80abvN0G58rTnkzo0uPqwahdwif79aS6fvf288WH-urj-8uLN1e16STkeuRSM4FjB8goZ0zoFRWyNdysYDTQN0IKoQchTVOmYYQcoOOG9g0yxlqG7KQ63_lultWMg0Gfo3ZqE-2s4w8VtFV_K97eqCncqqbnreh5MXi1N4jh64Ipq7lMrCTTHsOSVM-YhEa0rJAv_yHXYYm-pFMN0JYKwaFAZzvIxJBSxPHuKxTUtmG1bVgdGi43nv-Z4MDvKy0A2QPbmwc7rtpG0Z73XUFe_wdR4-Jcxu-5sM927DrlEO_gputkI4Qs-oudPuqg9BRtUtefSkAGlMuWs479Bt_m0Fc</recordid><startdate>20091020</startdate><enddate>20091020</enddate><creator>Sander, Edward A</creator><creator>Stylianopoulos, Triantafyllos</creator><creator>Tranquillo, Robert T</creator><creator>Barocas, Victor H</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091020</creationdate><title>Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels</title><author>Sander, Edward A ; 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Unraveling connections between externally applied loads and the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for examining the fine details of tissue behavior, but they require validation at multiple scales. In this study, we developed a multiscale model that captured the anisotropy and heterogeneity of a cell-compacted collagen gel subjected to an off-axis hold mechanical test and subsequently to biaxial extension. In both the model and experiments, the ECM reorganized in a nonaffine and heterogeneous manner that depended on multiscale interactions between the fiber networks. Simulations predicted that tensile and compressive fiber forces were produced to accommodate macroscopic displacements. Fiber forces in the simulation ranged from -11.3 to 437.7 nN, with a significant fraction of fibers under compression (12.1% during off-axis stretch). The heterogeneous network restructuring predicted by the model serves as an example of how multiscale modeling techniques provide a theoretical framework for understanding relationships between ECM structure and tissue-level mechanical properties and how microscopic fiber rearrangements could lead to mechanotransductive cell signaling.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>19805118</pmid><doi>10.1073/pnas.0903716106</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Anisotropy Biochemistry Biological Sciences Biomechanical Phenomena Cells Collagen Type I - chemistry Collagen Type I - physiology Collagens Compressive Strength - physiology Connective tissues Extracellular Matrix - chemistry Extracellular Matrix - physiology Fibroblasts Fibroblasts - physiology Fracture mechanics Gels Homeostasis - physiology Humans In Vitro Techniques Mechanical engineering Mechanics Mechanotransduction, Cellular - physiology Modeling Models, Biological Models, Molecular Multiprotein Complexes Multiscale modeling Parametric models Physical Sciences Proteins Signal Transduction - physiology Tensile Strength - physiology Tissues |
title | Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels |
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