title: Reversible Interactions of Proteins with Mixed Shell Polymeric Micelles: Tuning the Surface Hydrophobic/Hydrophilic Balance toward Efficient Artificial Chaperones.
abstract: Molecular chaperones can elegantly fine-tune its hydrophobic/hydrophilic balance to assist a broad spectrum of nascent polypeptide chains to fold properly. Such precious property is difficult to be achieved by chaperone mimicking materials due to limited control of their surface characteristics that dictate interactions with unfolded protein intermediates. Mixed shell polymeric micelles (MSPMs), which consist of two kinds of dissimilar polymeric chains in the micellar shell, offer a convenient way to fine-tune surface properties of polymeric nanoparticles. In the current work, we have fabricated ca. 30 kinds of MSPMs with finely tunable hydrophilic/hydrophobic surface properties. We investigated the respective roles of thermosensitive and hydrophilic polymeric chains in the thermodenaturation protection of proteins down to the molecular structure. Although the three kinds of thermosensitive polymers investigated herein can form collapsed hydrophobic domains on the micellar surface, we found distinct capability to capture and release unfolded protein intermediates, due to their respective affinity for proteins. Meanwhile, in terms of the hydrophilic polymeric chains in the micellar shell, poly(ethylene glycol) (PEG) excels in assisting unfolded protein intermediates to refold properly via interacting with the refolding intermediates, resulting in enhanced chaperone efficiency. However, another hydrophilic polymer-poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) severely deteriorates the chaperone efficiency of MSPMs, due to its protein-resistant properties. Judicious combination of thermosensitive and hydrophilic chains in the micellar shell lead to MSPM-based artificial chaperones with optimal efficacy.
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University , Tianjin 300071, P.R. China.
authors.forename: Jianzu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University , Tianjin 300071, P.R. China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Song
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University , Tianjin 300071, P.R. China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
authors.forename: Pingchuan
authors.initials: P
authors.lastname: Sun
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University , Tianjin 300071, P.R. China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: An
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University , Tianjin 300071, P.R. China.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University , Tianjin 300071, P.R. China.|State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300071, P.R. China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
authors.forename: Linqi
authors.initials: L
authors.lastname: Shi
mesh_terms: D040761:Biomimetic Materials; D024401:Carbonic Anhydrase I / Q000737:chemistry; D002942:Circular Dichroism; D000067493:Dynamic Light Scattering; D005026:Ethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011489:Protein Denaturation; D058849:Protein Refolding; D013499:Surface Properties; D013696:Temperature
chemical_list: D005026:Ethylene Glycols; D008823:Micelles; D011091:Polyesters; D011109:Polymethacrylic Acids; C115766:poly(2-methacryloyloxyethyl-phosphorylcholine); C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); C544117:poly(epsilon-caprolactone)-block-poly(2-(methacryloyloxy)ethyl phosphorylcholine); D010767:Phosphorylcholine; D024401:Carbonic Anhydrase I