Abstract
Branched actin network supports cell migration through extracellular microenvironments. However, it is unknown how intracellular proteins adapt the elastic properties of the network to the highly varying extracellular resistance. Here we develop a three-dimensional assembling model to simulate the realistic self-assembling process of the network by encompassing intracellular proteins and their dynamic interactions. Combining this multiscale model with finite element method, we reveal that the network can not only sense the variation of extracellular resistance but also self-adapt its elastic properties through remodeling with intracellular proteins. Such resistance-adaptive elastic behaviours are versatile and essential in supporting cell migration through varying extracellular microenvironments. The bending deformation mechanism and anisotropic Poisson’s ratios determine why lamellipodia persistently evolve into sheet-like structures. Our predictions are confirmed by published experiments. The revealed self-adaptive elastic properties of the networks are also applicable to the endocytosis, phagocytosis, vesicle trafficking, intracellular pathogen transport and dendritic spine formation.
Highlights
Branched actin network supports cell migration through extracellular microenvironments
The network is simplified to be linear elastic, the real structure shows viscoelastic behaviors[1,26]. Combining this multiscale assembling model with the finite element method (FEM), we have studied more than 4000 stochastic models of the lamellipodial actin network during cell migration
With our mathematical model, the in vivo microscopic spatial dynamic variation and reconfigurability of lamellipodial branched actin network, which are regulated by different intracellular proteins and variable confining extracellular microenvironments during cell migration, can be carefully simulated by regulating filamentous actin (F-actin) concentration, actin filament-polymerizing orientation, Arp2/3 complex successive branching, Arp2/3 complex branching density, and cross-linking proteins binding and unbinding, respectively or combinedly
Summary
Branched actin network supports cell migration through extracellular microenvironments It is unknown how intracellular proteins adapt the elastic properties of the network to the highly varying extracellular resistance. These dendritic subnetworks are cross-linked together by filamin-A and α-actinin, forming an interconnected branched actin network (Fig. 1)[1,10,11] In vivo, for both single cell and collective cells, their migrations based on lamellipodia are largely determined by the mechanical interactions between the lamellipodial branched actin networks and the confining extracellular microenvironments[1,8,12,13]. The networks’ complexity and stochastic biological process hinder one from performing an adequate number of biological experiments or carrying out mechanical analysis to study the quantitative relationships between the macroscopic elastic properties and the microscopic structures regulated by various intracellular proteins[22].
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