eprintid: 1447206 rev_number: 60 eprint_status: archive userid: 608 dir: disk0/01/44/72/06 datestamp: 2014-09-08 14:33:02 lastmod: 2024-07-03 11:01:17 status_changed: 2014-09-08 14:33:02 type: article metadata_visibility: show item_issues_count: 0 creators_name: Lewalle, A creators_name: Fritzsche, M creators_name: Wilson, K creators_name: Thorogate, R creators_name: Duke, T creators_name: Charras, G title: A phenomenological density-scaling approach to lamellipodial actin dynamics ispublished: pub divisions: UCL divisions: B04 divisions: C06 divisions: F64 keywords: lamellipodium, actin network, photoactivation, actin dynamics note: © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. abstract: The integration of protein function studied in vitro in a dynamic system like the cell lamellipodium remains a significant challenge. One reason is the apparent contradictory effects that perturbations of some proteins can have on the overall lamellipodium dynamics, depending on exact conditions. Theoretical modeling offers one approach for understanding the balance between the mechanisms that drive and regulate actin network growth and decay. Most models use a \bottom-up" approach, involving explicitly assembling biochemical components to simulate observable behaviour. Their correctness therefore relies on both the accurate characterisation of all the components and the completeness of the relevant processes involved. To avoid potential pitfalls due to this uncertainty, we used an alternative \top-down" approach, in which measurable features of lamellipodium behaviour, here observed in two different cell types (HL60 and B16-F1), directly inform the development of a simple phenomenological model of lamellipodium dynamics. We show that the kinetics of F-actin association and dissociation scales with the local F-actin density, with no explicit location dependence. This justifies the use of a simplified kinetic model of lamellipodium dynamics that yields predictions testable by pharmacological or genetic intervention. A length-scale parameter (the lamellipodium width), emerges from this analysis as an experimentally accessible probe of network regulatory processes. date: 2014-10-24 publisher: The Royal Society official_url: http://dx.doi.org/10.1098/rsfs.2014.0006 vfaculties: VMPS vfaculties: VMPS oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_source: Manually entered elements_id: 973142 doi: 10.1098/rsfs.2014.0006 lyricists_name: Charras, Guillaume lyricists_name: Duke, Thomas lyricists_name: Fritzsche, Marco lyricists_name: Lewalle, Alexandre lyricists_name: Thorogate, Richard lyricists_name: Wilson, Kerry lyricists_id: GCHAR39 lyricists_id: TAJDU21 lyricists_id: MFRIT58 lyricists_id: ALEWA97 lyricists_id: RTHOR67 lyricists_id: KWILS32 full_text_status: public publication: Interface Focus volume: 4 number: 6 article_number: 20140006 issn: 2042-8898 citation: Lewalle, A; Fritzsche, M; Wilson, K; Thorogate, R; Duke, T; Charras, G; (2014) A phenomenological density-scaling approach to lamellipodial actin dynamics. Interface Focus , 4 (6) , Article 20140006. 10.1098/rsfs.2014.0006 <https://doi.org/10.1098/rsfs.2014.0006>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1447206/2/LewalleEtAl_supplements.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1447206/3/20140006.full.pdf