Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries
An integrative cell migration model incorporating focal adhesion (FA) dynamics, cytoskeleton and nucleus remodeling, actin motor activity, and lamellipodia protrusion is developed for predicting cell spreading and migration behaviors. This work is motivated by two experimental works: (1) cell migrat...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2013
|
| Online Access: | http://hdl.handle.net/1721.1/78342 https://orcid.org/0000-0001-6649-9463 https://orcid.org/0000-0003-3155-6223 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1826205571982819328 |
|---|---|
| author | Kim, Min-Cheol Kamm, Roger Dale Neal, Devin M Asada, Haruhiko |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Kim, Min-Cheol Kamm, Roger Dale Neal, Devin M Asada, Haruhiko |
| author_sort | Kim, Min-Cheol |
| collection | MIT |
| description | An integrative cell migration model incorporating focal adhesion (FA) dynamics, cytoskeleton and nucleus remodeling, actin motor activity, and lamellipodia protrusion is developed for predicting cell spreading and migration behaviors. This work is motivated by two experimental works: (1) cell migration on 2-D substrates under various fibronectin concentrations and (2) cell spreading on 2-D micropatterned geometries. These works suggest (1) cell migration speed takes a maximum at a particular ligand density (~1140 molecules/µm2) and (2) that strong traction forces at the corners of the patterns may exist due to combined effects exerted by actin stress fibers (SFs). The integrative model of this paper successfully reproduced these experimental results and indicates the mechanism of cell migration and spreading. In this paper, the mechanical structure of the cell is modeled as having two elastic membranes: an outer cell membrane and an inner nuclear membrane. The two elastic membranes are connected by SFs, which are extended from focal adhesions on the cortical surface to the nuclear membrane. In addition, the model also includes ventral SFs bridging two focal adhesions on the cell surface. The cell deforms and gains traction as transmembrane integrins distributed over the outer cell membrane bond to ligands on the ECM surface, activate SFs, and form focal adhesions. The relationship between the cell migration speed and fibronectin concentration agrees with existing experimental data for Chinese hamster ovary (CHO) cell migrations on fibronectin coated surfaces. In addition, the integrated model is validated by showing persistent high stress concentrations at sharp geometrically patterned edges. This model will be used as a predictive model to assist in design and data processing of upcoming microfluidic cell migration assays. |
| first_indexed | 2024-09-23T13:15:15Z |
| format | Article |
| id | mit-1721.1/78342 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:15:15Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/783422022-10-01T14:01:40Z Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries Kim, Min-Cheol Kamm, Roger Dale Neal, Devin M Asada, Haruhiko Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. School of Engineering Singapore-MIT Alliance in Research and Technology (SMART) Kim, Min-Cheol Neal, Devin M. Kamm, Roger Dale Asada, Harry An integrative cell migration model incorporating focal adhesion (FA) dynamics, cytoskeleton and nucleus remodeling, actin motor activity, and lamellipodia protrusion is developed for predicting cell spreading and migration behaviors. This work is motivated by two experimental works: (1) cell migration on 2-D substrates under various fibronectin concentrations and (2) cell spreading on 2-D micropatterned geometries. These works suggest (1) cell migration speed takes a maximum at a particular ligand density (~1140 molecules/µm2) and (2) that strong traction forces at the corners of the patterns may exist due to combined effects exerted by actin stress fibers (SFs). The integrative model of this paper successfully reproduced these experimental results and indicates the mechanism of cell migration and spreading. In this paper, the mechanical structure of the cell is modeled as having two elastic membranes: an outer cell membrane and an inner nuclear membrane. The two elastic membranes are connected by SFs, which are extended from focal adhesions on the cortical surface to the nuclear membrane. In addition, the model also includes ventral SFs bridging two focal adhesions on the cell surface. The cell deforms and gains traction as transmembrane integrins distributed over the outer cell membrane bond to ligands on the ECM surface, activate SFs, and form focal adhesions. The relationship between the cell migration speed and fibronectin concentration agrees with existing experimental data for Chinese hamster ovary (CHO) cell migrations on fibronectin coated surfaces. In addition, the integrated model is validated by showing persistent high stress concentrations at sharp geometrically patterned edges. This model will be used as a predictive model to assist in design and data processing of upcoming microfluidic cell migration assays. 2013-04-11T14:45:12Z 2013-04-11T14:45:12Z 2013-02 2012-08 Article http://purl.org/eprint/type/JournalArticle 1553-734X 1553-7358 http://hdl.handle.net/1721.1/78342 Kim, Min-Cheol et al. “Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries.” Ed. Mark S. Alber. PLoS Computational Biology 9.2 (2013): e1002926. https://orcid.org/0000-0001-6649-9463 https://orcid.org/0000-0003-3155-6223 https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1371/journal.pcbi.1002926 PLoS Computational Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Kim, Min-Cheol Kamm, Roger Dale Neal, Devin M Asada, Haruhiko Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries |
| title | Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries |
| title_full | Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries |
| title_fullStr | Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries |
| title_full_unstemmed | Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries |
| title_short | Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries |
| title_sort | dynamic modeling of cell migration and spreading behaviors on fibronectin coated planar substrates and micropatterned geometries |
| url | http://hdl.handle.net/1721.1/78342 https://orcid.org/0000-0001-6649-9463 https://orcid.org/0000-0003-3155-6223 https://orcid.org/0000-0002-7232-304X |
| work_keys_str_mv | AT kimmincheol dynamicmodelingofcellmigrationandspreadingbehaviorsonfibronectincoatedplanarsubstratesandmicropatternedgeometries AT kammrogerdale dynamicmodelingofcellmigrationandspreadingbehaviorsonfibronectincoatedplanarsubstratesandmicropatternedgeometries AT nealdevinm dynamicmodelingofcellmigrationandspreadingbehaviorsonfibronectincoatedplanarsubstratesandmicropatternedgeometries AT asadaharuhiko dynamicmodelingofcellmigrationandspreadingbehaviorsonfibronectincoatedplanarsubstratesandmicropatternedgeometries |