Avoiding Macrophages: Design and Rationale Behind a 'marker of Self' Peptide

Macrophages are cells immediately available to combat wide range of pathogens without requiring prior exposure. They respond upon contact in a two-step process. In the first step, the macrophage is activated by contact to anything, even your own cells. In the second stage, and just before a macrophage engulfs its target, it checks for identification, that includes the 'marker of self' protein CD47, a widely expressed membrane protein. If CD47 is present, it causes the macrophage to disengage, making the activated phagocytosis process less efficient. Attachment of "self" CD47 on avidin-beads has shown a reduction in the rate of the phagocytosis by the macrophage.

Expression of CD47's functional domain is technically challenging, which encouraged us to search for a smaller peptide showing phagocytosis inhibition. We employed molecular dynamics simulations to understand the binding process and design a useful peptide based on the crystallographic structure of CD47/SIRP-α complex. We tested different peptides, each of them represent different strategies aiming to preserve the binding region structure. We found that some of these strategies maintained the structure better than others. Affinity experiments agreed with our predictions, and suggest the real possibility of more biocompatible materials with a small peptide.