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Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling

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Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling

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dc.contributor.author Zeng, Yukai
dc.contributor.author Lai, Tanny
dc.contributor.author Koh, Cheng Gee
dc.contributor.author LeDuc, Philip R.
dc.contributor.author Chiam, Keng-Hwee
dc.date.accessioned 2011-12-09T02:50:27Z
dc.date.available 2011-12-09T02:50:27Z
dc.date.copyright 2011
dc.date.issued 2011-12-09
dc.identifier.citation 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.
dc.identifier.issn 1542-0086
dc.identifier.uri http://hdl.handle.net/10220/7375
dc.description.abstract 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.
dc.format.extent 29 p.
dc.language.iso en
dc.relation.ispartofseries Biophysical journal
dc.rights © 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
dc.subject DRNTU::Science::Biological sciences::Biophysics
dc.title Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling
dc.type Journal Article
dc.contributor.department Library
dc.contributor.school School of Biological Sciences
dc.identifier.doi http://dx.doi.org/10.1016/j.bpj.2011.09.047
dc.description.version Accepted version
dc.identifier.rims 162375

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