Computational design of a minimal “protein-like” conjugate for potent membrane poration
Zhixiong Deng,
Xin You,
Bing Yuan,
Kai Yang
Affiliations
Zhixiong Deng
Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical Science and Technology, Soochow University, Suzhou 215006, China
Xin You
Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical Science and Technology, Soochow University, Suzhou 215006, China
Bing Yuan
Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical Science and Technology, Soochow University, Suzhou 215006, China; Jiangsu Key Laboratory of Thin Films, Soochow University, Suzhou 215006, China; Corresponding authors at: School of Physical Science and Technology, Soochow University, 1 Shizi, Suzhou, Jiangsu 215006, China.
Kai Yang
Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical Science and Technology, Soochow University, Suzhou 215006, China; Jiangsu Key Laboratory of Thin Films, Soochow University, Suzhou 215006, China; Corresponding authors at: School of Physical Science and Technology, Soochow University, 1 Shizi, Suzhou, Jiangsu 215006, China.
Biomimetic membrane nanopores have great potentials for bio- and nanotechnology applications. Here, a design strategy of an artificial protein by reasonably conjugating peptides and polymers for membrane poration was developed based on the α-helical bundle framework. A serial of peptide-polymer conjugates, composed of the α-helical peptide melittin (Mel) and clinically available polymer polyethylene glycol, were fabricated. Within them, the S-Mel, consisting of four helices arranged in a star-like bundle structure, demonstrated the most improved performance. Specifically, one single S-Mel molecule can build a stable membrane pore. Moreover, the obtained pores display stimuli-responsive properties in both size (including water flux) and structure, which is ascribed to the molecular architecture-regulated helical packing changes of S-Mel during membrane actions. These results promise S-Mel the ability to achieve ONOFF switching and gating effects for selective mass translocation across a cell membrane and help understand the structure-function relationship of proteins.
