Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments
Dimensionality is a fundamental component that can have profound implications on the characteristics of physical systems. In cell biology, however, the majority of studies on cell physical properties, from rheology to force generation to migration, have been performed on 2D substrates, and it is not...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2014
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| Online Access: | http://hdl.handle.net/1721.1/92473 https://orcid.org/0000-0002-6719-9929 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1826217721591758848 |
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| author | Mak, Michael Zaman, Muhammad H. Kamm, Roger Dale |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Mak, Michael Zaman, Muhammad H. Kamm, Roger Dale |
| author_sort | Mak, Michael |
| collection | MIT |
| description | Dimensionality is a fundamental component that can have profound implications on the characteristics of physical systems. In cell biology, however, the majority of studies on cell physical properties, from rheology to force generation to migration, have been performed on 2D substrates, and it is not clear how a more realistic 3D environment influences cell properties. Here, we develop an integrated approach and demonstrate the combination of mitochondria-tracking microrheology, microfluidics, and Brownian dynamics simulations to explore the impact of dimensionality on intracellular mechanics and on the effects of intracellular disruption. Additionally, we consider both passive thermal and active motor-driven processes within the cell and demonstrate through modeling how active internal fluctuations are modulated via dimensionality. Our results demonstrate that metastatic breast cancer cells (MDA-MB-231) exhibit more solid-like internal motions in 3D compared to 2D, and actin network disruption via Cytochalasin D has a more pronounced effect on internal cell fluctuations in 2D. Our computational results and modeling show that motor-induced active stress fluctuations are enhanced in 2D, leading to increased local intracellular particle fluctuations and apparent fluid-like behavior. |
| first_indexed | 2024-09-23T17:08:07Z |
| format | Article |
| id | mit-1721.1/92473 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:08:07Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/924732022-10-03T10:38:46Z Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments Mak, Michael Zaman, Muhammad H. Kamm, Roger Dale Massachusetts Institute of Technology. Department of Mechanical Engineering Mak, Michael Kamm, Roger Dale Dimensionality is a fundamental component that can have profound implications on the characteristics of physical systems. In cell biology, however, the majority of studies on cell physical properties, from rheology to force generation to migration, have been performed on 2D substrates, and it is not clear how a more realistic 3D environment influences cell properties. Here, we develop an integrated approach and demonstrate the combination of mitochondria-tracking microrheology, microfluidics, and Brownian dynamics simulations to explore the impact of dimensionality on intracellular mechanics and on the effects of intracellular disruption. Additionally, we consider both passive thermal and active motor-driven processes within the cell and demonstrate through modeling how active internal fluctuations are modulated via dimensionality. Our results demonstrate that metastatic breast cancer cells (MDA-MB-231) exhibit more solid-like internal motions in 3D compared to 2D, and actin network disruption via Cytochalasin D has a more pronounced effect on internal cell fluctuations in 2D. Our computational results and modeling show that motor-induced active stress fluctuations are enhanced in 2D, leading to increased local intracellular particle fluctuations and apparent fluid-like behavior. National Cancer Institute (U.S.) (Grant U01-CA177799) 2014-12-23T18:16:42Z 2014-12-23T18:16:42Z 2014-11 2014-07 Article http://purl.org/eprint/type/JournalArticle 1553-7358 1553-734X http://hdl.handle.net/1721.1/92473 Mak, Michael, Roger D. Kamm, and Muhammad H. Zaman. “Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments.” Edited by Andrew D. McCulloch. PLoS Comput Biol 10, no. 11 (November 20, 2014): e1003959. https://orcid.org/0000-0002-6719-9929 https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1371/journal.pcbi.1003959 PLoS Computational Biology Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Mak, Michael Zaman, Muhammad H. Kamm, Roger Dale Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments |
| title | Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments |
| title_full | Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments |
| title_fullStr | Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments |
| title_full_unstemmed | Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments |
| title_short | Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments |
| title_sort | impact of dimensionality and network disruption on microrheology of cancer cells in 3d environments |
| url | http://hdl.handle.net/1721.1/92473 https://orcid.org/0000-0002-6719-9929 https://orcid.org/0000-0002-7232-304X |
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