title: INSIGHTS INTO THE MECHANICS OF CYTOKINETIC RING ASSEMBLY USING 3D MODELING.
abstract: During fission yeast cytokinesis, actin filaments nucleated by cortical formin Cdc12 are captured by myosin motors bound to a band of cortical nodes. The myosin motors exert forces that pull nodes together into a contractile ring. Cross-linking interactions help align actin filaments and nodes into a single bundle. Mutations in the myosin motor domain and changes in the concentration of cross-linkers alpha-actinin and fimbrin alter the morphology of the condensing network, leading to clumps, rings or extended meshworks. How the contractile tension developing during ring formation depends on the interplay between network morphology, myosin motor activity, cross-linking and actin filament turnover remains to be elucidated. We addressed this question using a 3D computational model in which semiflexible actin filaments (represented as beads connected by springs) grow from formins, can be captured by myosin in neighboring nodes, and get cross-linked with one another through an attractive interaction. We identify regimes of tension generation between connected nodes under a wide set of conditions regarding myosin dynamics and strength of cross-linking between actin filaments. We find conditions that maximize circumferential tension, correlate them with network morphology and propose experiments to test these predictions. This work addresses "Morphogenesis of soft and living matter" using computational modeling to simulate cytokinetic ring assembly from the key molecular mechanisms of viscoelastic cross-linked actin networks that include active molecular motors.
authors.affiliation: Lehigh University, Bethlehem PA, USA.
authors.forename: Tamara Carla
authors.initials: TC
authors.lastname: Bidone
authors.affiliation: Lehigh University, Bethlehem PA, USA.
authors.forename: Haosu
authors.initials: H
authors.lastname: Tang
authors.affiliation: Lehigh University, Bethlehem PA, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Vavylonis
references.citation: J Phys Condens Matter. 2011 Sep 21;23(37):374103
references.pmid: 21862839
references.citation: Science. 2008 Jan 4;319(5859):97-100
references.pmid: 18079366
references.citation: Dev Cell. 2014 Jun 9;29(5):547-61
references.pmid: 24914559
references.citation: J Cell Biol. 2013 Oct 14;203(1):101-14
references.pmid: 24127216
references.citation: Mol Biol Cell. 2012 Aug;23(16):3094-110
references.pmid: 22740629
references.citation: Curr Biol. 2012 Sep 11;22(17):1601-8
references.pmid: 22840513