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Tailoring Biomimetic Phosphorylcholine-Containing Block Copolymers as Membrane-Targeting Cellular Rescue Agents



Jia-Yu Wang, Wei Chen, Michihiro Nagao, Phullara Shelat, Brenton A. G. Hammer, Gregory T. Tietjen, Kathleen Cao, J. Michael Henderson, Lilin He, Binhua Lin, Bulent Akgun, Mati Meron, Shuo Qian, Sarah Ward, Jeremy D. Marks, Todd Emrick, Ka Yee C. Lee


Some synthetic polymers have been found capable of rescuing injured cells from death by targeting cell membranes. However, general principles for designing synthetic polymers to ensure strong, but non-disruptive cell membrane targeting unknown. Here, we establish new design principles by tailoring biomimetic phosphorylcholine-containing block copolymers to target cell membranes and rescue neutrons from injury. By precisely altering the hydrophilicity and membrane affinity of poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC)-based triblock copolymers, we have determined the membrane interactions responsible for rescuing injured neurons from death. This cellular rescue capability is attributed to non-intrusive polymer-membrane interactions. These interactions alter the collective dynamics of the cell membrane by inducing modest membrane rigidification, without disrupting lipid packing or membrane thickness. Our results open a new avenues for biomedical applications of polyMPC-based polymers, and highlight a general paradigm for the rational design of membrane-targeting cellular rescue agents.


Phosphorylcholine-containing polymer, cellular rescue agent, membrane elasticity, membrane structure and dynamics


Wang, J. , Chen, W. , Nagao, M. , Shelat, P. , Hammer, B. , Tietjen, G. , Cao, K. , Henderson, J. , He, L. , Lin, B. , Akgun, B. , Meron, M. , Qian, S. , Ward, S. , Marks, J. , Emrick, T. and Lee, K. (2019), Tailoring Biomimetic Phosphorylcholine-Containing Block Copolymers as Membrane-Targeting Cellular Rescue Agents, Biomacromolecules, [online], (Accessed April 16, 2024)
Created September 8, 2019, Updated October 12, 2021