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Antagonist Effects of l-Phenylalanine and the Enantiomeric Mixture Containing d-Phenylalanine on Phospholipid Vesicle Membrane

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    Antagonist Effects of l-Phenylalanine and the Enantiomeric Mixture Containing d-Phenylalanine on Phospholipid Vesicle Membrane
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    • Sourav Nandi
      Sourav Nandi
      Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India
      More by Sourav Nandi
    • Arghajit Pyne
      Arghajit Pyne
      Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India
      More by Arghajit Pyne
    • Meghna Ghosh
      Meghna Ghosh
      Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India
      More by Meghna Ghosh
    • Pavel Banerjee
      Pavel Banerjee
      Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India
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    • Biswajoy Ghosh
      Biswajoy Ghosh
      School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302, India
      More by Biswajoy Ghosh
      Orcidhttp://orcid.org/0000-0003-1309-1661
    • Nilmoni Sarkar*
      Nilmoni Sarkar
      Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India
      *E-mail: [email protected] or [email protected]. Fax: 91-3222-255303.
      More by Nilmoni Sarkar
      Orcidhttp://orcid.org/0000-0002-8714-0000
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    Langmuir

    Cite this: Langmuir 2020, 36, 9, 2459–2473
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    https://doi.org/10.1021/acs.langmuir.9b03543
    Published February 19, 2020
    Copyright © 2020 American Chemical Society
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    Abstract

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    One of the congenital flaws of metabolism, phenylketonuria (PKU), is known to be related to the self-assembly of toxic fibrillar aggregates of phenylalanine (Phe) in blood at elevated concentrations. Our experimental findings using l-phenylalanine (l-Phe) at millimolar concentration suggest the formation of fibrillar morphologies in the dry phase, which in the solution phase interact strongly with the model membrane composed of 1,2-diacyl-sn-glycero-phosphocholine (LAPC) lipid, thereby decreasing the rigidity (or increasing the fluidity) of the membrane. The hydrophobic interaction, in addition to the electrostatic attraction of Phe with the model membrane, is found to be responsible for such phenomena. On the contrary, various microscopic observations reveal that such fibrillar morphologies of l-Phe are severely ruptured in the presence of its enantiomer d-phenylalanine (d-Phe), thereby converting the fibrillar morphologies into crushed flakes. Various biophysical studies, including the solvation dynamics experiment, suggest that this l-Phe in the presence of d-Phe, when interacting with the same model membrane, now reverts the rigidity of the membrane, i.e., increases the rigidity of the membrane, which was lost due to interaction with l-Phe exclusively. Fluorescence anisotropy measurements also support this reverse rigid character of the membrane in the presence of an enantiomeric mixture of amino acids. A comprehensive understanding of the interaction of Phe with the model membrane is further pursued at the single-molecular fluorescence detection level using fluorescence correlation spectroscopy (FCS) experiments. Therefore, our experimental conclusion interprets a linear correlation between increased permeability and enhanced fluidity of the membrane in the presence of l-Phe and certifies d-Phe as a therapeutic modulator of l-Phe fibrillar morphologies. Further, the study proposes that the rigidity of the membrane lost due to interaction with l-Phe was reinstated—in fact, increased—in the presence of the enantiomeric mixture containing both d- and l-Phe.

    Copyright © 2020 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.langmuir.9b03543.

    • Instrumental details; viscosity measurement of water pool of lipid vesicle using FLIM images; cell culture and viability assay protocol; calculation for affinity constant of Phe to the model membrane; FESEM and FLIM images of Phe fibrils; FLIM images of vesicle and lifetime distribution histogram of DCM dye inside vesicle in the absence and presence of Phe; fluorescence emission spectra of thioflavin T in the fibrils; size distribution and polydispersity index of the vesicle solution in the presence of Phe; DLS plots of fibrils; zeta potential of membrane in the presence of Phe; tabular form for the comparison of the effect of l-Phe and d-Phe on LAPC lipid membrane; ITC plots; and MTT assay (PDF)

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    This article is cited by 23 publications.

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    Langmuir

    Cite this: Langmuir 2020, 36, 9, 2459–2473
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.langmuir.9b03543
    Published February 19, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

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