Journal
BIOMACROMOLECULES
Volume 20, Issue 9, Pages 3385-3391Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.9b00621
Keywords
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Funding
- NSF [MCB-0920316, MCB-1413613, DMR-0944772, NSF-MRSECDMR-0820506]
- University of Chicago NSF-MRSEC program [DMR-0820054, DMR1420709]
- U.S. Department of Energy, Office of Science, Materials Science and Engineering Division
- NIH Health Grants [R01 NS 056313, T32 HL -094282]
- NIST, U.S. Department of Commerce [70NANB15H2S9]
- DOE, the Office of Biological and Environmental Research
- DOE, the Scientific User Facilities Division, Office of Basic Energy Sciences
- NSF/DOE [CHE0087817]
- DOE, Basic Energy Sciences, and Office of Science [W-31-109-Eng-38]
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Some synthetic polymers can block cell death when applied following an injury that would otherwise kill the cell. This cellular rescue occurs through interactions of the polymers with cell membranes. However, general principles for designing synthetic polymers to ensure strong, but nondisruptive, cell membrane targeting are not fully elucidated. Here, we tailored biomimetic phosphorylcholine-containing block copolymers to interact with cell membranes and determined their efficacy in blocking neuronal death following oxygen-glucose deprivation. By adjusting the hydrophilicity and membrane affinity of poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC)-based triblock copolymers, the surface active regime in which the copolymers function effectively as membrane-targeting cellular rescue agents was determined. We identified nonintrusive interactions between the polymer and the cell membrane that alter the collective dynamics of the membrane by inducing rigidification without disrupting lipid packing or membrane thickness. In general, our results open new avenues for biological applications of polyMPC-based polymers and provide an approach to designing membrane-targeting agents to block cell death after injury.
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