Modeling Population Dynamics of Antimicrobial Peptides in Bacterial Culture

Antimicrobial peptides (AMPs) are broad-spectrum antibiotics that utilize electrostatics to target bacteria selectively. Despite our knowledge of the molecular structure and membrane interactions of AMPs, their population dynamics are still poorly understood. We developed a model that quantifies the kinetics of AMPs that inhibits the growth of a bacterial culture by considering the binary state for individual cells’ physiology: (1) natural growth and (2) fully inhibited growth. These simulations are inspired by our experimental data where the minimum inhibitory concentration (MIC) of AMPs is dependent on the cell density. We hypothesize that bacteria killed by AMP LL-37 absorb additional AMPs, thus effectively reducing the available concentration of AMPs' for attacking the remaining cells. Our model recapitulates the experimental behavior and suggests that dead bacteria absorb on the order of 10⁸ AMPs. Furthermore, our model allows us to infer a few parameters that are not accessible from direct experimental measurements. Specifically, we can quantify the killing rate of bacteria and the number of AMPs sequestered by each individual cells.