Understanding the Lamellipodium

Understanding the Lamellipodium - A Mathematical Approach

Simulation Results

3D Leading Edge Model

Leading Edge

C. Winkler, C. Schmeiser

EM - Pictures combined with filament tracking

Filaments are stiff rods

Includes branching and capping

Interaction between membrane and filaments

Geometry (curvature) plays a central role

Model assumptions give an explanation for the flatness of the lamellipodium

x

Flatness of the

Lamellipodium

C. Schmeiser, C. Winkler. The flatness of lamellipodia explained by the interaction between actin dynamics and membrane deformation. submitted. 2014

S. Koestler, C. Auinger, M. Vinzenz, K. Rottner and J.V. Small. Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front. Nature Cell Biology. 2008

C. Winkler, M. Vinzenz, J.V. Small and C. Schmeiser. Actin filament tracking in electron tomogramsof negatively stained lamellipodia using the localized radon transform. Journal of Structural Biology. 2012

Symmetry Breaking and Chemotaxis

Chemotaxis

Symmetry Breaking

A white blood cell chasing a bacteria

Spontaneous polarization in a fish keratocyte

Maths

Bundle Model

Model Formulation

S. Hirsch, D. Ölz, C. Schmeiser

Whole Cell

Shape Changes

Full Mathematical Model

Incudes actin filament and their polymerization

Includes bundeling proteins

Describes myosin pulling effects

2D Whole Cell Model

A. Manhart, C. Schmeiser, D. Ölz, N. Sfakianakis

Two Filament Families

Filaments cannot be bent too much

Adhesions form with the substrate

Filament number and length are regulated

Polymerization speed is regulated

Myosin pulling from the inside

D. Ölz, C. Schmeiser, How do cells move? Mathematical modelling of cytoskeleton dynamics and cell migration. Cell mechanics: from single scale-based models to multiscale modelling. 2010

A. Manhart, C. Schmeiser, D. Ölz, N. Sfakianakis. An Extended Filament Based Lamellipodium Model Produces Various Moving Cell Shapes in the Presence of Chemotactic Signals. submitted. 2015

Simulation Results II

D. Ölz, C. Schmeiser. Simulation of lamellipodial fragments. Journal of Mathematical Biology. 2012

Simulation Results I

The Team

Mathematics & Simulation

Biology & Experiments

Group Leader

Group Leaders

Actin Flow Rates

Right: A. Wilson et al. Myosin II contributes to cell-scale actin network treadmilling through network disassembly. Nature Letters. 2010

Christian Schmeiser (University of Vienna, Austria)

Michael Sixt (IST Austria)

Vic Small (IMBA)

Modelling and Simulation

Experiments and Imaging

Adhesive Stripes - Comparison

Right:

G. Csus, K. Quirin, G. Danuser. Locomotion of Fish Epidermal Keratocytes on Spatially Selective Adhesion Patterns. Cell Motility and the Cytoskeleton. 2007

Jan Müller

Maria Nemethova

Stefanie Hirsch

Christoph Winkler

Angelika Manhart

Dietmar Ölz

Nikolaos Sfakianakis

Angelika Manhart (angelika.manhart@univie.ac.at)