Force generation by endocytic actin patches in budding yeast - PubMed (original) (raw)

Force generation by endocytic actin patches in budding yeast

Anders E Carlsson et al. Biophys J. 2014.

Abstract

Membrane deformation during endocytosis in yeast is driven by local, templated assembly of a sequence of proteins including polymerized actin and curvature-generating coat proteins such as clathrin. Actin polymerization is required for successful endocytosis, but it is not known by what mechanisms actin polymerization generates the required pulling forces. To address this issue, we develop a simulation method in which the actin network at the protein patch is modeled as an active gel. The deformation of the gel is treated using a finite-element approach. We explore the effects and interplay of three different types of force driving invagination: 1), forces perpendicular to the membrane, generated by differences between actin polymerization rates at the edge of the patch and those at the center; 2), the inherent curvature of the coat-protein layer; and 3), forces parallel to the membrane that buckle the coat protein layer, generated by an actomyosin contractile ring. We find that with optimistic estimates for the stall stress of actin gel growth and the shear modulus of the actin gel, actin polymerization can generate almost enough force to overcome the turgor pressure. In combination with the other mechanisms, actin polymerization can the force over the critical value.

Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1

Schematic of proposed force-generation mechanisms for actin-driven endocytosis. Black arrows denote forces exerted by the actin network on coat-proteins/membrane, and gray arrows denote forces exerted by coat proteins/membrane on the actin network. (a) Vertical forces caused by actin polymerization in the outer region or actomyosin contraction in the central region. (b) Spontaneous bending of the coat-protein layer. (c) Horizontal forces resulting from contraction of actomyosin around the coat-protein layer.

Figure 2

Figure 2

(a) Dependence of the actin polymerization rate factor αp on radial coordinate R. (b) Dependence of the actin polymerization rate factor γp on stress σzz; v∞=−0.05.

Figure 3

Figure 3

Three-dimensional view of invagination induced by actin polymerization at time t=3 time units. Colors (see scale at right) denote vertical displacement, in units of 10−8m. σ0=104Pa; other parameters have baseline values (Table 1), except that P0=5×104Pa. To see this figure in color, go online.

Figure 4

Figure 4

(a) Growth profile in actin gel, after 1 time unit of growth. Colors (see scale at right) denote growth G zZ, which is dimensionless. Parameters: σ0=104Pa, other parameters have baseline values (Table 1), except for P0=5×104Pa. (b) Stress distribution in actin gel after 1 time unit of growth. Stress (colors) is given in units of 105Pa. Parameters are as in a. (c) Same as b, but after 3 time units. To see this figure in color, go online.

Figure 5

Figure 5

Displacement at the center of the endocytic site as a function of time. Parameters are baseline values, except that P0=5×104Pa and σ0=104Pa.

Figure 6

Figure 6

(a) Indentation distance, Δz, after 5 time units of simulation, as function of actin stall stress, σ0. (b) Pressure at the center of the endocytic site after 5 time units of simulation, as a function of σ0. Parameters are baseline parameters (Table 1) unless otherwise indicated. Alternate symbols show effects of decreasing turgor pressure, P0 (squares), or actin shear modulus, μa (triangles).

Figure 7

Figure 7

(a) Energy change from coat-protein deformation (dashed line) pushing against turgor pressure (dotted line), and their sum (solid line). Energies are given in 10−18J. Parameters: turgor pressure, P0=2×105Pa, and κc=1.56×10−18J are chosen so that the initial slope of total energy vanishes. Dot-dashed line gives total energy when P0=105Pa. (b) Energy change from myosin contraction, with T=400pN.

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