Rule-based modelling provides an extendable framework for comparing candidate mechanisms underpinning clathrin polymerisation

Abstract Polymerisation of clathrin is a key process that underlies clathrin-mediated endocytosis. Clathrin-coated vesicles are responsible for cell internalization of external substances required for normal homeostasis and life –sustaining activity. There are several hypotheses describing formation of closed clathrin structures. According to one of the proposed mechanisms cage formation may start from a flat lattice buildup on the cellular membrane, which is later transformed into a curved structure. Creation of the curved surface requires rearrangement of the lattice, induced by additional molecular mechanisms. Different potential mechanisms require a modeling framework that can be easily modified to compare between them. We created an extendable rule-based model that describes polymerisation of clathrin molecules and various scenarios of cage formation. Using Global Sensitivity Analysis (GSA) we obtained parameter sets describing clathrin pentagon closure and the emergence/production and closure of large-size clathrin cages/vesicles. We were able to demonstrate that the model can reproduce budding of the clathrin cage from an initial flat array

Coarse-grained simulations of entangled star polyethylene melts

In this paper, a previous coarse-grain model [J. T. Padding and W. J. Briels, J. Chem. Phys. 117, 925 (2002)]10.1063/1.1481859 to simulate melts of linear polymers has been adapted to simulate polymers with more complex hierarchies. Bond crossings between highly coarse-grained soft particles are prevented by applying an entanglement algorithm. We first test our method on a virtual branch point inside a linear chain to make sure it works effectively when linking two linear arms. Next, we apply our method to study the diffusive and rheological behaviors of a melt of three-armed stars. We find that the diffusive behavior of the three-armed star is very close to that of a linear polymer with the same molecular weight, while its rheological properties are close to those of a linear chain with molecular mass equal to that of the longest linear sub-chain in the star

A cost–benefit analysis of the physical mechanisms of membrane curvature

Many cellular membrane-bound structures exhibit distinct curvature that is driven by the physical properties of their lipid and protein constituents. Here we review how cells manipulate and control this curvature in the context of dynamic events such as vesicle-mediated membrane traffic. Lipids and cargo proteins each contribute energetic barriers that must be overcome during vesicle formation. In contrast, protein coats and their associated accessory proteins drive membrane bending using a variety of interdependent physical mechanisms. We survey the energetic costs and drivers involved in membrane curvature, drawing a contrast between the stochastic contributions of molecular crowding and the deterministic assembly of protein coats. These basic principles also apply to other cellular examples of membrane bending events, including important disease-related problems like viral egress