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dc.contributor.authorKim, Min-Cheol
dc.contributor.authorSilberberg, Yaron R.
dc.contributor.authorWhisler, Jordan Ari
dc.contributor.authorKamm, Roger Dale
dc.contributor.authorAsada, Harry
dc.date.accessioned2015-11-05T17:58:50Z
dc.date.available2015-11-05T17:58:50Z
dc.date.issued2015-10
dc.date.submitted2015-04
dc.identifier.issn1553-7358
dc.identifier.issn1553-734X
dc.identifier.urihttp://hdl.handle.net/1721.1/99731
dc.description.abstractThe dynamics of filopodia interacting with the surrounding extracellular matrix (ECM) play a key role in various cell-ECM interactions, but their mechanisms of interaction with the ECM in 3D environment remain poorly understood. Based on first principles, here we construct an individual-based, force-based computational model integrating four modules of 1) filopodia penetration dynamics; 2) intracellular mechanics of cellular and nuclear membranes, contractile actin stress fibers, and focal adhesion dynamics; 3) structural mechanics of ECM fiber networks; and 4) reaction-diffusion mass transfers of seven biochemical concentrations in related with chemotaxis, proteolysis, haptotaxis, and degradation in ECM to predict dynamic behaviors of filopodia that penetrate into a 3D ECM fiber network. The tip of each filopodium crawls along ECM fibers, tugs the surrounding fibers, and contracts or retracts depending on the strength of the binding and the ECM stiffness and pore size. This filopodium-ECM interaction is modeled as a stochastic process based on binding kinetics between integrins along the filopodial shaft and the ligands on the surrounding ECM fibers. This filopodia stochastic model is integrated into migratory dynamics of a whole cell in order to predict the cell invasion into 3D ECM in response to chemotaxis, haptotaxis, and durotaxis cues. Predicted average filopodia speed and that of the cell membrane advance agreed with experiments of 3D HUVEC migration at r[superscript 2] > 0.95 for diverse ECMs with different pore sizes and stiffness.en_US
dc.description.sponsorshipSingapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology)en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Science and Technology Center and Emergent Behaviors of Integrated Cellular Systems (Grant EFRI-0735997)en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Science and Technology Center and Emergent Behaviors of Integrated Cellular Systems (Grant STC-0902396)en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Science and Technology Center and Emergent Behaviors of Integrated Cellular Systems (Grant CBET-0939511)en_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pcbi.1004535en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourcePublic Library of Scienceen_US
dc.titleCell Invasion Dynamics into a Three Dimensional Extracellular Matrix Fibre Networken_US
dc.typeArticleen_US
dc.identifier.citationKim, Min-Cheol, Jordan Whisler, Yaron R. Silberberg, Roger D. Kamm, and H. Harry Asada. “Cell Invasion Dynamics into a Three Dimensional Extracellular Matrix Fibre Network.” Edited by Cynthia A. Reinhart-King. PLoS Comput Biol 11, no. 10 (October 5, 2015): e1004535.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineeringen_US
dc.contributor.mitauthorKim, Min-Cheolen_US
dc.contributor.mitauthorWhisler, Jordan Arien_US
dc.contributor.mitauthorKamm, Roger Daleen_US
dc.contributor.mitauthorAsada, Harryen_US
dc.relation.journalPLOS Computational Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsKim, Min-Cheol; Whisler, Jordan; Silberberg, Yaron R.; Kamm, Roger D.; Asada, H. Harryen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-3299-9424
dc.identifier.orcidhttps://orcid.org/0000-0001-6649-9463
dc.identifier.orcidhttps://orcid.org/0000-0003-3155-6223
dc.identifier.orcidhttps://orcid.org/0000-0002-7232-304X
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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