Dynamic Modeling of Antimicrobial Pore Formation in Engineered Tethered Membranes

In this paper, a mesoscopic-to-observable dynamic model of the pore formation measurement platform is presented. The platform is composed of a controllable engineered tethered membrane. Using the mesoscopic-to-observable model and experimental measurements allows the platform to be used to gain insight into the pore formation dynamics of peptides in biological membranes. These results are useful for the development of novel drugs, gene delivery therapies, and controlling pore formation in cell-like bioreactors. The model consists of coarse-grained molecular dynamics, a continuum model composed of a generalized version of Fick´s law of diffusion coupled with surface reaction-diffusion equations, and a fractional order macroscopic model. We consider the pore formation dynamics of the antimicrobial peptide PGLa using the dynamic model and experimental measurements from the platform. The results provide a possible reaction-mechanism for PGLa pore formation in charged and uncharged membranes, which accounts for binding, translocation, and oligomerization of PGLa. The reaction-mechanism suggests that PGLa not only increases the number of pores in negatively charged membranes, but also increases the lifetime of pores compared to PGLa pores in uncharged membranes. Though results for PGLa are presented, the dynamics model and platform can be used to investigate the pore formation dynamics of other peptides.