Characterizing deformability and surface friction of cancer cells
Metastasis requires the penetration of cancer cells through tight spaces, which is mediated by the physical properties of the cells as well as their interactions with the confined environment. Various microfluidic approaches have been devised to mimic traversal in vitro by measuring the time require...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
National Academy of Sciences (U.S.)
2014
|
| Online Access: | http://hdl.handle.net/1721.1/88251 https://orcid.org/0000-0001-5223-9433 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-3415-3614 https://orcid.org/0000-0003-4110-1388 https://orcid.org/0000-0003-4165-7538 https://orcid.org/0000-0001-5277-6060 |
| _version_ | 1826206821089542144 |
|---|---|
| author | Byun, Sangwon Son, Sungmin Amodei, Dario Cermak, Nathan Shaw, Josephine Kang, Joon Ho Hecht, Vivian Chaya Mallick, Parag Winslow, Monte Meier Jacks, Tyler E Manalis, Scott R |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Byun, Sangwon Son, Sungmin Amodei, Dario Cermak, Nathan Shaw, Josephine Kang, Joon Ho Hecht, Vivian Chaya Mallick, Parag Winslow, Monte Meier Jacks, Tyler E Manalis, Scott R |
| author_sort | Byun, Sangwon |
| collection | MIT |
| description | Metastasis requires the penetration of cancer cells through tight spaces, which is mediated by the physical properties of the cells as well as their interactions with the confined environment. Various microfluidic approaches have been devised to mimic traversal in vitro by measuring the time required for cells to pass through a constriction. Although a cell’s passage time is expected to depend on its deformability, measurements from existing approaches are confounded by a cell's size and its frictional properties with the channel wall. Here, we introduce a device that enables the precise measurement of (i) the size of a single cell, given by its buoyant mass, (ii) the velocity of the cell entering a constricted microchannel (entry velocity), and (iii) the velocity of the cell as it transits through the constriction (transit velocity). Changing the deformability of the cell by perturbing its cytoskeleton primarily alters the entry velocity, whereas changing the surface friction by immobilizing positive charges on the constriction's walls primarily alters the transit velocity, indicating that these parameters can give insight into the factors affecting the passage of each cell. When accounting for cell buoyant mass, we find that cells possessing higher metastatic potential exhibit faster entry velocities than cells with lower metastatic potential. We additionally find that some cell types with higher metastatic potential exhibit greater than expected changes in transit velocities, suggesting that not only the increased deformability but reduced friction may be a factor in enabling invasive cancer cells to efficiently squeeze through tight spaces. |
| first_indexed | 2024-09-23T13:38:46Z |
| format | Article |
| id | mit-1721.1/88251 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:38:46Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/882512022-10-01T16:14:19Z Characterizing deformability and surface friction of cancer cells Byun, Sangwon Son, Sungmin Amodei, Dario Cermak, Nathan Shaw, Josephine Kang, Joon Ho Hecht, Vivian Chaya Mallick, Parag Winslow, Monte Meier Jacks, Tyler E Manalis, Scott R Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Department of Physics Koch Institute for Integrative Cancer Research at MIT Byun, Sangwon Son, Sungmin Cermak, Nathan Shaw, Josephine Kang, Joon Ho Hecht, Vivian Chaya Winslow, Monte M. Jacks, Tyler E. Manalis, Scott R. Metastasis requires the penetration of cancer cells through tight spaces, which is mediated by the physical properties of the cells as well as their interactions with the confined environment. Various microfluidic approaches have been devised to mimic traversal in vitro by measuring the time required for cells to pass through a constriction. Although a cell’s passage time is expected to depend on its deformability, measurements from existing approaches are confounded by a cell's size and its frictional properties with the channel wall. Here, we introduce a device that enables the precise measurement of (i) the size of a single cell, given by its buoyant mass, (ii) the velocity of the cell entering a constricted microchannel (entry velocity), and (iii) the velocity of the cell as it transits through the constriction (transit velocity). Changing the deformability of the cell by perturbing its cytoskeleton primarily alters the entry velocity, whereas changing the surface friction by immobilizing positive charges on the constriction's walls primarily alters the transit velocity, indicating that these parameters can give insight into the factors affecting the passage of each cell. When accounting for cell buoyant mass, we find that cells possessing higher metastatic potential exhibit faster entry velocities than cells with lower metastatic potential. We additionally find that some cell types with higher metastatic potential exhibit greater than expected changes in transit velocities, suggesting that not only the increased deformability but reduced friction may be a factor in enabling invasive cancer cells to efficiently squeeze through tight spaces. National Cancer Institute (U.S.) (Contract CCNE-T (Grant 26697290-47281-A)) National Cancer Institute (U.S.) (Physical Sciences Oncology Center U54CA143874) Stand Up To Cancer (SU2C/AACR) 2014-07-10T19:11:13Z 2014-07-10T19:11:13Z 2013-04 2012-10 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/88251 Byun, S., S. Son, D. Amodei, N. Cermak, J. Shaw, J. H. Kang, V. C. Hecht, et al. “Characterizing Deformability and Surface Friction of Cancer Cells.” Proceedings of the National Academy of Sciences 110, no. 19 (May 7, 2013): 7580–7585. https://orcid.org/0000-0001-5223-9433 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-3415-3614 https://orcid.org/0000-0003-4110-1388 https://orcid.org/0000-0003-4165-7538 https://orcid.org/0000-0001-5277-6060 en_US http://dx.doi.org/10.1073/pnas.1218806110 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Byun, Sangwon Son, Sungmin Amodei, Dario Cermak, Nathan Shaw, Josephine Kang, Joon Ho Hecht, Vivian Chaya Mallick, Parag Winslow, Monte Meier Jacks, Tyler E Manalis, Scott R Characterizing deformability and surface friction of cancer cells |
| title | Characterizing deformability and surface friction of cancer cells |
| title_full | Characterizing deformability and surface friction of cancer cells |
| title_fullStr | Characterizing deformability and surface friction of cancer cells |
| title_full_unstemmed | Characterizing deformability and surface friction of cancer cells |
| title_short | Characterizing deformability and surface friction of cancer cells |
| title_sort | characterizing deformability and surface friction of cancer cells |
| url | http://hdl.handle.net/1721.1/88251 https://orcid.org/0000-0001-5223-9433 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-3415-3614 https://orcid.org/0000-0003-4110-1388 https://orcid.org/0000-0003-4165-7538 https://orcid.org/0000-0001-5277-6060 |
| work_keys_str_mv | AT byunsangwon characterizingdeformabilityandsurfacefrictionofcancercells AT sonsungmin characterizingdeformabilityandsurfacefrictionofcancercells AT amodeidario characterizingdeformabilityandsurfacefrictionofcancercells AT cermaknathan characterizingdeformabilityandsurfacefrictionofcancercells AT shawjosephine characterizingdeformabilityandsurfacefrictionofcancercells AT kangjoonho characterizingdeformabilityandsurfacefrictionofcancercells AT hechtvivianchaya characterizingdeformabilityandsurfacefrictionofcancercells AT mallickparag characterizingdeformabilityandsurfacefrictionofcancercells AT winslowmontemeier characterizingdeformabilityandsurfacefrictionofcancercells AT jackstylere characterizingdeformabilityandsurfacefrictionofcancercells AT manalisscottr characterizingdeformabilityandsurfacefrictionofcancercells |