The co-assembly of peptides with lipid membranes is important in both healthy and diseased states. On one hand, the immune system uses self-assembling antimicrobial peptides to capture pathogens and help rid them from the body. On the other hand, peptide and lipid co-assembly has been proposed to be important in the progression of protein aggregation diseases such as Alzheimer’s and Parkinson’s. We study this important phenomenon using a peptide fragment of the seminal protein prostatic phosphatase (PAP_248-286). Strikingly, PAP_248-286 forms fibrillar amyloid aggregates that enhance the infectivity of many enveloped viruses, including HIV. Therefore, the amyloid form of PAP_248-286 was named a semen-derived enhancer of viral infection, or SEVI. While SEVI fibrils seem to be important in the spread of some sexually transmitted diseases, they also display antimicrobial activity through their ability to agglutinate pathogenic bacteria and appear to participate in sperm quality control. Our study finds that, in addition to forming amyloid, PAP_248-286 can also assemble with artificial negatively charged liposomes to form large, heterogenous co-aggregates that we have affectionately termed “messicles” (short for “mess of vesicles”).

The cover image for the September 1 issue of Biophysical Journal shows a negative stain transmission electron microscopy micrograph of a messicle. We thought that messicles resembled some of the captivating images of nebulae from the Hubble Space Telescope. While they are vastly different in size — messicles are on the micrometer scale while nebulae are measured in light-years — nebulae and messicles are somewhat similar: Just like nebulae are amorphous self-assemblies of gasses and dust, messicles are amorphous assemblies of the peptide PAP_248-286 with anionic liposomes. This led us to our artistic re-imagining of a messicle as a nebula, colorizing the micrograph and adding a starfield to the background.  

Our paper focuses on determining the conditions under which messicles form, characterizing them, and trying to understand their formation mechanism. We believe it is possible that some or all of the biological activities assigned to SEVI could be mediated by messicles, and that similar formation mechanisms could apply to other biologically important peptide and lipid co-assemblies.

- Eleanor W. Vane, Shushan He, Lutz Maibaum, Abhinav Nath