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Emergence of Large-Scale Cell Morphology and Movement from Local Actin Filament Growth Dynamics

Figure 6

Mathematical Modeling Explains the Coherent and Decoherent Keratocyte Phenotypes

(A) In coherent cells, long actin filaments are protected from capping and undergo significant lateral flow (arrows), smoothing heterogeneities at the leading edge. According to the Graded Radial Extension model, Vn(x)=V cosθ, where V represents cell speed, Vn represents the local protrusion rate, and θ is the orientation of the normal to the leading edge at position x. Quantitative actin dynamics (right) are explained in the Materials and Methods and Text S1.

(B) In decoherent cells, short filaments that are not protected from capping undergo less-extensive lateral flow (arrows) and may focus into heterogeneities at the leading edge causing the unstable protrusion of microregions.

(C) Barbed end density and nascent filament branching were chosen so that when VASP activity is low, the F-actin density along the leading edge appears flat (bottom curve). When high VASP activity was entered into our model, the F-actin density along the leading edge emerged as an inverted parabola (top curve), with F-actin density peaked in the middle, as observed experimentally in coherent cells. Position is normalized by the half-length of the leading edge. The prediction that peaked F-actin density is proportional to the level of VASP is qualitatively consistent with the experiment (see Figures 4C and 4D).

(D) Based on protrusion rate as a function of barbed end distribution along the leading edge, the computed leading edge profile is wide (canoe-shaped) in coherent cells with high VASP at the leading edge (top curve) and short (D shaped) in decoherent cells with low VASP at the leading edge (bottom curve). Position (x) is normalized by the half-length of the leading edge of the short, decoherent cell. The same scale is used for the coherent cell, which is 30% longer, so the corresponding profile extends beyond 1.

Figure 6