Biopolymer model generalizes predictions of self-assembly processes

During biopolymer self-assembly, free monomers assemble to form metastable intermediates on their way to becoming stable polymers. When a monomer joins the end of an intermediate, it assumes the same configurational state as the monomer it attaches to. However, the rest of the intermediate polymer chain may have different internal configurations, and each monomer interacts with its neighbors to autocatalytically convert until the entire chain reaches a conformationally homogeneous stable state.

Typically, models consider this ordering process instantaneous for mathematical convenience, but experimental evidence indicates that it occurs on timescales comparable to other processes. Taylor et al. developed a model that treats the ordering as a dynamic, time-dependent process, allowing for the quantitative prediction of conformationally mixed intermediates that have been linked to diseases such as Alzheimer’s and Parkinson’s.

The model is distinct in its consideration of metastable intermediate interactions, including the elongation of the chain and the propagation of the stable state, which compete over time and can induce large changes in the system.

“While existing models have made tremendous contributions to our understanding of experimental data, until we incorporated these dynamics, we were unable to explain features such as mixed intermediates and transitions between different dynamical regimes that are likely to play a crucial role in disease,” said author Alexander Taylor.

By explicitly including these nonequilibrium dynamics, the model can predict distinct self-assembly regimes, including one characterized by the accumulation of morphologically diverse intermediates, which the authors believe occurs in Alzheimer’s and Parkinson’s.

Though the model agrees well with experimental data, Taylor noted additional testing is necessary to better understand some of its unanticipated predictions about the size and composition of metastable intermediates.

Source: “A two-step biopolymer nucleation model shows a nonequilibrium critical point,” by Alexander I. P. Taylor, Lianne D. Gahan, Buddhapriya Chakrabarti, and Rosemary A. Staniforth, Journal of Chemical Physics (2020). The article can be accessed at https://doi.org/10.1063/5.0009394 .