Actin Filaments Couple the Protrusive Tips to the Nucleus through the I-BAR Domain Protein IRSp53 during the Migration of Cells on 1D Fibers
| dc.contributor.author | Mukherjee, Apratim | en |
| dc.contributor.author | Ron, Jonathan Emanuel | en |
| dc.contributor.author | Hu, Hooi Ting | en |
| dc.contributor.author | Nishimura, Tamako | en |
| dc.contributor.author | Hanawa-Suetsugu, Kyoko | en |
| dc.contributor.author | Behkam, Bahareh | en |
| dc.contributor.author | Mimori-Kiyosue, Yuko | en |
| dc.contributor.author | Gov, Nir Shachna | en |
| dc.contributor.author | Suetsugu, Shiro | en |
| dc.contributor.author | Nain, Amrinder Singh | en |
| dc.date.accessioned | 2023-06-27T19:10:43Z | en |
| dc.date.available | 2023-06-27T19:10:43Z | en |
| dc.date.issued | 2023-03 | en |
| dc.description.abstract | The cell migration cycle, well-established in 2D, proceeds with forming new protrusive structures at the cell membrane and subsequent redistribution of contractile machinery. Three-dimensional (3D) environments are complex and composed of 1D fibers, and 1D fibers are shown to recapitulate essential features of 3D migration. However, the establishment of protrusive activity at the cell membrane and contractility in 1D fibrous environments remains partially understood. Here the role of membrane curvature regulator IRSp53 is examined as a coupler between actin filaments and plasma membrane during cell migration on single, suspended 1D fibers. IRSp53 depletion reduced cell-length spanning actin stress fibers that originate from the cell periphery, protrusive activity, and contractility, leading to uncoupling of the nucleus from cellular movements. A theoretical model capable of predicting the observed transition of IRSp53-depleted cells from rapid stick-slip migration to smooth and slower migration due to reduced actin polymerization at the cell edges is developed, which is verified by direct measurements of retrograde actin flow using speckle microscopy. Overall, it is found that IRSp53 mediates actin recruitment at the cellular tips leading to the establishment of cell-length spanning fibers, thus demonstrating a unique role of IRSp53 in controlling cell migration in 3D. | en |
| dc.description.sponsorship | This work was supported by grants from the JSPS (KAKENHI JP20H03252, JP20KK0341, and JP21H05047) and JST CREST (JPMJCR1863) to S.S, and JST CREST (JPMJCR1863) to Y.M.K. N.S.G. is the incumbent of the Lee and William Abramowitz Professorial Chair of Biophysics and acknowledges support by the Ben May Center for Theory and Computation and the Israel Science Foundation (Grant No. 207/22). This research was made possible in part by the historic generosity of the Harold Perlman Family. A.S.N. acknowledges partial funding support from National Science Foundation (NSF, Grant No. 1762468 and 2119949). A.S.N. and B.B. acknowledge the Institute of Critical Technologies and Science (ICTAS) and Macromolecules Innovative Institute (MII) at Virginia Tech for their support in conducting this study. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | https://doi.org/10.1101/2022.05.20.492840 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/115546 | en |
| dc.identifier.volume | 10 | en |
| dc.language.iso | en | en |
| dc.publisher | Wiley-VCH | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | actin | en |
| dc.subject | cell forces | en |
| dc.subject | extracellular matrice nanofibers | en |
| dc.subject | IRSp53 | en |
| dc.subject | membrane curvature | en |
| dc.subject | protrusions | en |
| dc.subject | stick-slip migration | en |
| dc.title | Actin Filaments Couple the Protrusive Tips to the Nucleus through the I-BAR Domain Protein IRSp53 during the Migration of Cells on 1D Fibers | en |
| dc.title.serial | Advanced Science | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |