Year: 2017
Type: article
Abstract: We present a Master Equation approach to calculating polymerization dynamics and force generation by branched actin networks at membranes.The method treats the time evolution of the F-actin distribution in three dimensions, with branching included as a directional spreading term.It is validated by comparison with stochastic simulations of force generation by actin polymerization at obstacles coated with actin "nucleation promoting factors" (NPFs).The method is then used to treat the dynamics of actin polymerization and force generation during endocytosis in yeast, using a model in which NPFs form a ring around the endocytic site, centered by a spot of molecules attaching the actin network strongly to the membrane.We find that a spontaneous actin filament nucleation mechanism is required for adequate forces to drive the process, that partial inhibition of branching and polymerization lead to different characteristic responses, and that a limited range of polymerization-rate values provide effective invagination and obtain correct predictions for the effects of mutations in the active regions of the NPFs. Author summaryEndocytosis is a dynamic process by which cells internalize substances from outside the cell.Especially in yeast, endocytosis is mechanically demanding due to the high pressure difference across the cell membrane, or turgor pressure.Polymerization of a branched actin network is the major process providing the mechanical force to overcome the turgor pressure.Understanding the kinetics of the actin network, and the mechanical interaction between the actin network and the cell membrane, is thus crucial for the study of endocytosis.We develop an efficient mathematical framework for actin dynamics that can realistically incorporate these two features, thus providing a practical method for quantitatively modeling actin dynamics during endocytosis.The resulting model mechanistically reveals that spontaneous nucleation at the center of the endocytic site is required for successful endocytosis, distinguishes the roles of branching and polymerization, and predicts several other experimentally testable outcomes.The accuracy and efficiency of the method, in describing both mechanics and chemistry, render it applicable to a broad field of membrane-bending processes.
Source: PLoS Computational Biology
Authors: Xinxin Wang, Anders E. Carlsson
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
OpenAlex ID: W2772615199