Molecular 'hole punchers' and Their Mechanisms: from Synthetic Antimicrobials to HIV Protein Transduction Domains
Gerard CL Wong
Department of Materials Science and Engineering, Department of Physics, Department of Bioengineering, University of Illinois
Antimicrobial peptides comprise a key component of innate immunity for a wide range of multicellular organisms. It has been shown that natural antimicrobial peptides and their analogs can permeate bacterial membranes but not host membranes. There are a number of proposed models for this action, but the detailed molecular mechanism of the induced membrane permeation remains unclear. We investigate interactions between model bacterial membranes and a prototypical family of phenylene ethynylene-based antimicrobials with controllable hydrophilic and hydrophobic volume fractions, and controllable charge placement. We show how these antimicrobials punch holes in bacterial membranes and examine the mechanism for selectivity. We show that the general principles governing the action of these membrane active antimicrobials are cognate to natural antimicrobial peptides as well as protein transduction domains such as the transacting transcriptional activator (TAT) from the HIV virus, and penetratin from the fruit fly.
