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 D. 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

doi:10.1021/acs.biomac.9b00621

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 D. 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

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	3385-3391
Number of pages	7
Journal	Biomacromolecules
Volume	20
Issue number	9
DOIs	https://doi.org/10.1021/acs.biomac.9b00621
State	Published - Sep 9 2019

Funding

We thank Xiangji Chen for providing polyMPC homopolymers Yun Liu for assistance with SANS measurements, and Paul D. Butler for valuable discussions. J.-Y.W., G.T.T., K.D.C., J.M.H., and K.Y.C.L. acknowledge the support of the NSF (MCB-0920316 and MCB-1413613) and the University of Chicago NSF-MRSEC program (DMR-0820054 and DMR-1420709). W.C. gratefully acknowledges the financial support from the U.S. Department of Energy, Office of Science, Materials Science and Engineering Division. P.S. and J.D.M. acknowledge the support of NIH Health Grants (R01 NS-056313 and T32 HL-094282). B.A.G.H. and T.E. acknowledge funding from the NSF-supported UMass MRSEC on Polymers and the Materials Research Facilities Network (NSF-MRSEC-DMR-0820506). M.N. acknowledges funding from cooperative agreement 70NANB15H259 from NIST, U.S. Department of Commerce. We acknowledge the support of NIST, DOC, in providing the neutron research facilities used in this work. Access to the NG5-NSE was provided by the Center for High Resolution Neutron Scattering a partnership between the National Institute of Standards and Technology and the National Science Foundation under Agreement No. DMR-1508259. The Bio-SANS instrument used in this study is a resource of the Center for Structural Molecular Biology at ORNL, which is supported by DOE the Office of Biological and Environmental Research. Bio-SANS is located at ORNL-HFIR, which is sponsored by DOE, the Scientific User Facilities Division, Office of Basic Energy Sciences. ChemMatCARS is principally supported by the NSF/DOE (CHE-0087817). The APS is supported by the DOE, Basic Energy Sciences, and Office of Science (W-31-109-Eng-38). The work also utilized the Materials Research Facilities Network (MRFN-DMR-5-44456) and facilities supported in part by the NSF (DMR-0944772). We thank Xiangji Chen for providing polyMPC homopolymers, Yun Liu for assistance with SANS measurements, and Paul D. Butler for valuable discussions. J.-Y.W., G.T.T., K.D.C., J.M.H., and K.Y.C.L. acknowledge the support of the NSF (MCB-0920316 and MCB-1413613) and the University of Chicago NSF-MRSEC program (DMR-0820054 and DMR-1420709). W.C. gratefully acknowledges the financial support from the U.S. Department of Energy, Office of Science, Materials Science and Engineering Division. P.S. and J.D.M. acknowledge the support of NIH Health Grants (R01 NS-056313 and T32 HL-094282). B.A.G.H. and T.E. acknowledge funding from the NSF-supported UMass MRSEC on Polymers and the Materials Research Facilities Network (NSF-MRSEC-DMR-0820506). M.N. acknowledges funding from cooperative agreement 70NANB15H259 from NIST, U.S. Department of Commerce. We acknowledge the support of NIST, DOC, in providing the neutron research facilities used in this work. Access to the NG5-NSE was provided by the Center for High Resolution Neutron Scattering, a partnership between the National Institute of Standards and Technology and the National Science Foundation under Agreement No. DMR-1508259. The Bio-SANS instrument used in this study is a resource of the Center for Structural Molecular Biology at ORNL, which is supported by DOE, the Office of Biological and Environmental Research. Bio-SANS is located at ORNL-HFIR, which is sponsored by DOE, the Scientific User Facilities Division, Office of Basic Energy Sciences. ChemMatCARS is principally supported by the NSF/DOE (CHE-0087817). The APS is supported by the DOE, Basic Energy Sciences, and Office of Science (W-31-109-Eng-38). The work also utilized the Materials Research Facilities Network (MRFN-DMR-5-44456) and facilities supported in part by the NSF (DMR-0944772).

Funders	Funder number
Center for High Resolution Neutron Scattering
Center for Structural Molecular Biology at ORNL
Materials Research Facilities Network	NSF-MRSEC-DMR-0820506, 70NANB15H259
Materials Science and Engineering Division
NIH Health
NSF-supported UMass MRSEC
NSF-supported UMass MRSEC on Polymers and the Materials Research Facilities Network
NSF/DOE	CHE-0087817
Office of Basic Energy Sciences
Office of Biological and Environmental Research
Scientific User Facilities Division
University of Chicago NSF-MRSEC	DMR-1420709, DMR-0820054
National Science Foundation	DMR-1508259, 1834750
National Institutes of Health	R01 NS-056313, T32 HL-094282
U.S. Department of Energy
National Institute of Standards and Technology
U.S. Department of Commerce
California Department of Conservation
Office of Science
Basic Energy Sciences	W-31-109-Eng-38, MRFN-DMR-5-44456, DMR-0944772
American Pain Society

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Wang, J. Y., Chen, W., Nagao, M., Shelat, P., Hammer, B. A. G., Tietjen, G. T., Cao, K. D., Henderson, J. M., He, L., Lin, B., Akgun, B., Meron, M., Qian, S., Ward, S., Marks, J. D., Emrick, T., & Lee, K. Y. C. (2019). Tailoring Biomimetic Phosphorylcholine-Containing Block Copolymers as Membrane-Targeting Cellular Rescue Agents. Biomacromolecules, 20(9), 3385-3391. https://doi.org/10.1021/acs.biomac.9b00621

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title = "Tailoring Biomimetic Phosphorylcholine-Containing Block Copolymers as Membrane-Targeting Cellular Rescue Agents",

abstract = "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.",

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

note = "Publisher Copyright: Copyright {\textcopyright} 2019 American Chemical Society.",

year = "2019",

month = sep,

day = "9",

doi = "10.1021/acs.biomac.9b00621",

language = "English",

volume = "20",

pages = "3385--3391",

journal = "Biomacromolecules",

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Wang, JY, Chen, W, Nagao, M, Shelat, P, Hammer, BAG, Tietjen, GT, Cao, KD, Henderson, JM, He, L, Lin, B, Akgun, B, Meron, M, Qian, S, Ward, S, Marks, JD, Emrick, T & Lee, KYC 2019, 'Tailoring Biomimetic Phosphorylcholine-Containing Block Copolymers as Membrane-Targeting Cellular Rescue Agents', Biomacromolecules, vol. 20, no. 9, pp. 3385-3391. https://doi.org/10.1021/acs.biomac.9b00621

TY - JOUR

T1 - Tailoring Biomimetic Phosphorylcholine-Containing Block Copolymers as Membrane-Targeting Cellular Rescue Agents

AU - Wang, Jia Yu

AU - Chen, Wei

AU - Nagao, Michihiro

AU - Shelat, Phullara

AU - Hammer, Brenton A.G.

AU - Tietjen, Gregory T.

AU - Cao, Kathleen D.

AU - Henderson, J. Michael

AU - He, Lilin

AU - Lin, Binhua

AU - Akgun, Bulent

AU - Meron, Mati

AU - Qian, Shuo

AU - Ward, Sarah

AU - Marks, Jeremy D.

AU - Emrick, Todd

AU - Lee, Ka Yee C.

PY - 2019/9/9

Y1 - 2019/9/9

N2 - 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.

AB - 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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SN - 1525-7797

VL - 20

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EP - 3391

JO - Biomacromolecules

JF - Biomacromolecules

IS - 9

ER -

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

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