It is highly desired to have bioactive surfaces for biomaterials and controllable interactions with cells. These functions were widely achieved by attaching functional peptides to the surface of biomaterials. It is well known that an antifouling layer can help reducing the nonspecific cell attachment. However, it is unclear how an antifouling PEG layer affects the function of peptides attached on material surface in controlling cell behavior. This highlight introduced the recent JACS paper from Prof. Liu and coworkers in addressing this question thoroughly.