Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling
Circular dorsal ruffles (CDRs) are transient actin-rich ring-like structures which form on the dorsal surface of growth-factor stimulated cells. However, the dynamics and mechanism of formation of CDRs are still unknown. It has been observed that CDR formation leads to stress fibers disappearing nea...
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| Format: | Journal Article |
| Language: | English |
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2011
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| Online Access: | https://hdl.handle.net/10356/93636 http://hdl.handle.net/10220/7375 |
| _version_ | 1824454605009846272 |
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| author | LeDuc, Philip R. Zeng, Yukai Lai, Tanny Koh, Cheng Gee Chiam, Keng-Hwee |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences LeDuc, Philip R. Zeng, Yukai Lai, Tanny Koh, Cheng Gee Chiam, Keng-Hwee |
| author_sort | LeDuc, Philip R. |
| collection | NTU |
| description | Circular dorsal ruffles (CDRs) are transient actin-rich ring-like structures which form on the dorsal surface of growth-factor stimulated cells. However, the dynamics and mechanism of formation of CDRs are still unknown. It has been observed that CDR formation leads to stress fibers disappearing near the CDRs. Since stress fiber formation can be modified by substrate stiffness, we examined the effect of substrate stiffness on CDR formation by seeding NIH 3T3 fibroblasts on glass and polydimethylsiloxane (PDMS) substrates of varying stiffnesses from 20 kPa to 1800 kPa. We found that increasing substrate stiffness increased the lifetime of the CDRs. We developed a mathematical model of the signaling pathways involved in CDR formation to provide insight into this lifetime and size dependence which is linked to substrate stiffness via Rac-Rho antagonism. From the model, increasing stiffness raised mDia1-nucleated stress fiber formation due to Rho activation. The increased stress fibers present increased replenishment of the G-actin pool, therefore prolonging Arp2/3-nucleated CDR formation due to Rac activation. Negative feedback by WAVE-related RacGAP on Rac explained how CDR actin propagates as an excitable wave, much like wave propagation in other excitable medium, e.g., nerve signal transmission. |
| first_indexed | 2025-02-19T03:24:58Z |
| format | Journal Article |
| id | ntu-10356/93636 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:24:58Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | ntu-10356/936362023-02-28T17:03:41Z Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling LeDuc, Philip R. Zeng, Yukai Lai, Tanny Koh, Cheng Gee Chiam, Keng-Hwee School of Biological Sciences Library DRNTU::Science::Biological sciences::Biophysics Circular dorsal ruffles (CDRs) are transient actin-rich ring-like structures which form on the dorsal surface of growth-factor stimulated cells. However, the dynamics and mechanism of formation of CDRs are still unknown. It has been observed that CDR formation leads to stress fibers disappearing near the CDRs. Since stress fiber formation can be modified by substrate stiffness, we examined the effect of substrate stiffness on CDR formation by seeding NIH 3T3 fibroblasts on glass and polydimethylsiloxane (PDMS) substrates of varying stiffnesses from 20 kPa to 1800 kPa. We found that increasing substrate stiffness increased the lifetime of the CDRs. We developed a mathematical model of the signaling pathways involved in CDR formation to provide insight into this lifetime and size dependence which is linked to substrate stiffness via Rac-Rho antagonism. From the model, increasing stiffness raised mDia1-nucleated stress fiber formation due to Rho activation. The increased stress fibers present increased replenishment of the G-actin pool, therefore prolonging Arp2/3-nucleated CDR formation due to Rac activation. Negative feedback by WAVE-related RacGAP on Rac explained how CDR actin propagates as an excitable wave, much like wave propagation in other excitable medium, e.g., nerve signal transmission. Accepted version 2011-12-09T02:50:27Z 2019-12-06T18:42:47Z 2011-12-09T02:50:27Z 2019-12-06T18:42:47Z 2011 2011 Journal Article Zeng, Y., Lai, T., Koh, C. G., LeDuc, P. R., Chiam, K.-H. (2011). Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modelling. Biophysical journal, 101(9), 2122-2130. 1542-0086 https://hdl.handle.net/10356/93636 http://hdl.handle.net/10220/7375 10.1016/j.bpj.2011.09.047 22067149 162375 en Biophysical journal © 2011 The Biophysical society. This is the author created version of a work that has been peer reviewed and accepted for publication by Biophysical Journal, The Biophysical society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: http://dx.doi.org/10.1016/j.bpj.2011.09.047 29 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Biophysics LeDuc, Philip R. Zeng, Yukai Lai, Tanny Koh, Cheng Gee Chiam, Keng-Hwee Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling |
| title | Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling |
| title_full | Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling |
| title_fullStr | Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling |
| title_full_unstemmed | Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling |
| title_short | Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling |
| title_sort | investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling |
| topic | DRNTU::Science::Biological sciences::Biophysics |
| url | https://hdl.handle.net/10356/93636 http://hdl.handle.net/10220/7375 |
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