Building a dendritic actin filament network branch by branch: models of filament orientation pattern and force generation in lamellipodia

Abstract

We review mathematical and computational models of the structure, dynamics, and force generation properties of dendritic actin networks. These models have been motivated by the dendritic nucleation model, which provided a mechanistic picture of how the actin cytoskeleton system powers cell motility. We describe how they aimed to explain the self-organization of the branched network into a bimodal distribution of filament orientations peaked at 35°and − 35°with respect to the direction of membrane protrusion, as well as other patterns. Concave and convex force-velocity relationships were derived, depending on network organization, filament, and membrane elasticity and accounting for actin polymerization at the barbed end as a Brownian ratchet. This review also describes models that considered the kinetics and transport of actin and diffuse regulators and mechanical coupling to a substrate, together with explicit modeling of dendritic networks.

Lamellipodium tip actin barbed ends serve as a force sensor

“…Neither the WAVE complex nor Ena/VASP proteins are essential in the stretch-induced tip actin polymerization. These relationships are in agreement with the force-velocity relationship predicted by the BR mechanism although the results do not distinguish among BR models predicting similar exponential force-velocity curves (Mogilner & Oster, 1996, 2003Peskin et al, 1993) and more complex models incorporating the BR force-velocity relationship (Carlsson, 2003;Holz & Vavylonis, 2018).…”

4polar-STORM polarized super-resolution imaging of actin filament organization in cells

“…The variations in the precise distribution of actin filament orientations at the cell edge, and the non-negligible presence of 3D orientations, are consistent with recent findings in the literature based on EM and modelling 4 . A range of angular distributions of actin filament orientations has been evidenced, which appears to be more complex and heterogeneous than a pure bimodal distribution with peaks positioned at the 70° branching angle 53 .…”

“…Adhesion of animal cells to the extracellular matrix is driven, for example, by dramatic conformational changes in force-sensing and force-transducing proteins such as integrins and talins. The precise geometry of actin filament assemblies 1,2,3,4,5 and its remodelling in space and time are further determinant for cell mechanics driving essential biological processes, including immune responses and tissue development. Thus, understanding the function of a protein and its interaction with its partners, necessitates that we observe its organization at the nanometer scale, both in position and orientation.…”

A mechanism with severing near barbed ends and annealing explains structure and dynamics of dendritic actin networks

“…Gray lines: actin filaments; red: Arp2/3 complex; yellow:free barbed ends; orange: capped barbed ends; blue: free pointed ends. results (Holz and Vavylonis, 2018). Atilgan et al (Atilgan et al, 2005) reported that obtaining the ±35 • pattern requires restricting branching to occur primarily along the lamellipodium plane, which they attributed to structural constraints of the branching machinery at the leading edge.…”

“…This dendritic lamellipodia network structure, evident in electron micrographs of keratocytes (Svitkina et al, 1997) has been quantified by more recent electron tomograms near the leading edge, revealing the number of barbed ends, branches and filaments (Mueller et al, 2017;Vinzenz et al, 2012). Its characteristic pattern with filaments orientated primarily at ±35 • with respect to the protrusion axis (Koseki et al, 2019;Maly and Borisy, 2002;Mueller et al, 2017;Schaub et al, 2007) has been interpreted by two dimensional dendritic network models (Atilgan et al, 2005;Holz and Vavylonis, 2018;Maly and Borisy, 2002;Schaus et al, 2007;Weichsel and Schwarz, 2010).…”