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Cell Migration in 1D and 2D Nanofiber Microenvironments
Understanding how cells migrate in fibrous environments is important in wound healing, immune function, and cancer progression. A key question is how fiber orientation and network geometry influence cell movement. Here we describe a quantitative, modeling-based approach toward identifying the mechan...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809563/ https://www.ncbi.nlm.nih.gov/pubmed/29150767 http://dx.doi.org/10.1007/s10439-017-1958-6 |
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author | Estabridis, Horacio M. Jana, Aniket Nain, Amrinder Odde, David J. |
author_facet | Estabridis, Horacio M. Jana, Aniket Nain, Amrinder Odde, David J. |
author_sort | Estabridis, Horacio M. |
collection | PubMed |
description | Understanding how cells migrate in fibrous environments is important in wound healing, immune function, and cancer progression. A key question is how fiber orientation and network geometry influence cell movement. Here we describe a quantitative, modeling-based approach toward identifying the mechanisms by which cells migrate in fibrous geometries having well controlled orientation. Specifically, U251 glioblastoma cells were seeded onto non-electrospinning Spinneret based tunable engineering parameters fiber substrates that consist of networks of suspended 400 nm diameter nanofibers. Cells were classified based on the local fiber geometry and cell migration dynamics observed by light microscopy. Cells were found in three distinct geometries: adhering two a single fiber, adhering to two parallel fibers, and adhering to a network of orthogonal fibers. Cells adhering to a single fiber or two parallel fibers can only move in one dimension along the fiber axis, whereas cells on a network of orthogonal fibers can move in two dimensions. We found that cells move faster and more persistently in 1D geometries than in 2D, with cell migration being faster on parallel fibers than on single fibers. To explain these behaviors mechanistically, we simulated cell migration in the three different geometries using a motor-clutch based model for cell traction forces. Using nearly identical parameter sets for each of the three cases, we found that the simulated cells naturally replicated the reduced migration in 2D relative to 1D geometries. In addition, the modestly faster 1D migration on parallel fibers relative to single fibers was captured using a correspondingly modest increase in the number of clutches to reflect increased surface area of adhesion on parallel fibers. Overall, the integrated modeling and experimental analysis shows that cell migration in response to varying fibrous geometries can be explained by a simple mechanical readout of geometry via a motor-clutch mechanism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10439-017-1958-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5809563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-58095632018-02-22 Cell Migration in 1D and 2D Nanofiber Microenvironments Estabridis, Horacio M. Jana, Aniket Nain, Amrinder Odde, David J. Ann Biomed Eng Article Understanding how cells migrate in fibrous environments is important in wound healing, immune function, and cancer progression. A key question is how fiber orientation and network geometry influence cell movement. Here we describe a quantitative, modeling-based approach toward identifying the mechanisms by which cells migrate in fibrous geometries having well controlled orientation. Specifically, U251 glioblastoma cells were seeded onto non-electrospinning Spinneret based tunable engineering parameters fiber substrates that consist of networks of suspended 400 nm diameter nanofibers. Cells were classified based on the local fiber geometry and cell migration dynamics observed by light microscopy. Cells were found in three distinct geometries: adhering two a single fiber, adhering to two parallel fibers, and adhering to a network of orthogonal fibers. Cells adhering to a single fiber or two parallel fibers can only move in one dimension along the fiber axis, whereas cells on a network of orthogonal fibers can move in two dimensions. We found that cells move faster and more persistently in 1D geometries than in 2D, with cell migration being faster on parallel fibers than on single fibers. To explain these behaviors mechanistically, we simulated cell migration in the three different geometries using a motor-clutch based model for cell traction forces. Using nearly identical parameter sets for each of the three cases, we found that the simulated cells naturally replicated the reduced migration in 2D relative to 1D geometries. In addition, the modestly faster 1D migration on parallel fibers relative to single fibers was captured using a correspondingly modest increase in the number of clutches to reflect increased surface area of adhesion on parallel fibers. Overall, the integrated modeling and experimental analysis shows that cell migration in response to varying fibrous geometries can be explained by a simple mechanical readout of geometry via a motor-clutch mechanism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10439-017-1958-6) contains supplementary material, which is available to authorized users. Springer US 2017-11-17 2018 /pmc/articles/PMC5809563/ /pubmed/29150767 http://dx.doi.org/10.1007/s10439-017-1958-6 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Estabridis, Horacio M. Jana, Aniket Nain, Amrinder Odde, David J. Cell Migration in 1D and 2D Nanofiber Microenvironments |
title | Cell Migration in 1D and 2D Nanofiber Microenvironments |
title_full | Cell Migration in 1D and 2D Nanofiber Microenvironments |
title_fullStr | Cell Migration in 1D and 2D Nanofiber Microenvironments |
title_full_unstemmed | Cell Migration in 1D and 2D Nanofiber Microenvironments |
title_short | Cell Migration in 1D and 2D Nanofiber Microenvironments |
title_sort | cell migration in 1d and 2d nanofiber microenvironments |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809563/ https://www.ncbi.nlm.nih.gov/pubmed/29150767 http://dx.doi.org/10.1007/s10439-017-1958-6 |
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