title: A phenomenological density-scaling approach to lamellipodial actin dynamics(†).
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 effect that perturbations of some proteins can have on the overall lamellipodium dynamics, depending on exact conditions. Theoretical modelling 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 characterization 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.
authors.affiliation: London Centre for Nanotechnology , University College London , 17-19 Gordon Street, London WC1H 0AH , UK.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lewalle
authors.affiliation: London Centre for Nanotechnology , University College London , 17-19 Gordon Street, London WC1H 0AH , UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Fritzsche
authors.affiliation: London Centre for Nanotechnology , University College London , 17-19 Gordon Street, London WC1H 0AH , UK.
authors.forename: Kerry
authors.initials: K
authors.lastname: Wilson
authors.affiliation: London Centre for Nanotechnology , University College London , 17-19 Gordon Street, London WC1H 0AH , UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Thorogate
authors.affiliation: London Centre for Nanotechnology , University College London , 17-19 Gordon Street, London WC1H 0AH , UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Duke
authors.affiliation: London Centre for Nanotechnology , University College London , 17-19 Gordon Street, London WC1H 0AH , UK ; Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK ; Institute for the Physics of Living Systems, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charras
keywords: actin dynamics; actin network; lamellipodium; photoactivation