Machine learning of the anomalous diffusion of branched polymers in crosslinked networks

Abstract

Diffusion processes in complex environments, such as the extracellular matrix, are crucial in drug delivery. Common analytical theories developed for diffusion in such environments assume spherical, rigid particles. However, polymeric nanoparticles can often be aspherical and highly deformable, which introduces complexity beyond the spherical and rigid body assumptions. Moreover, it is challenging to measure classical diffusion coefficients under strong confinement or pronounced sub-diffusive conditions. We theoretically investigate the diffusion of branched polymers (bottlebrushes and stars) in polymeric mesh networks using coarse-grained molecular dynamics simulations. We introduce the Debye–Waller factor, a metric of confined mobility that we prove predicts long-time diffusion. We show that in relevant confinement regimes, elongated bottlebrushes have higher mobility than spherical stars. We can reliably predict the Debye–Waller factor from particle and network descriptors using Gaussian process regression. These results characterise the diffusion of arbitrary branched polymer nanoparticles and provide new, easily obtained metrics and protocols to design more efficient drug delivery carriers based on simple physical principles.