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. 2021 May 27;15(1):36.
doi: 10.1186/s13065-021-00763-0.

Hyaluronic acid-lipid binding

Anthony Ewurum #  1 , Abhishek Ashok Alur #  2 , Margaret Glenn #  2 , Abigail Schnepf  1 , Douglas Borchman  3
Affiliations

Hyaluronic acid-lipid binding

Anthony Ewurum et al. BMC Chem. .

Abstract

Background: Phospholipid (PL)-hyaluronic acid (HA) interactions are relevant to aging-associated vitreous humor liquefaction, therapies for dry eye disease, skin-care products and synovial joint lubrication. Phosphatidyl choline-HA interactions have been well characterized. However, other major lipids found in tears, vitreous humor and synovial joints have not. The purpose of this study was to bridge this gap of knowledge.

Methods: HA (1600 kDa) at 5 mg/mL, was mixed with various lipids ranging in concentration from 0.1 to 10 mg/mL in D2O. HA-PL binding was measured from the decrease in HA proton resonance intensity with binding using a nuclear magnetic resonance spectrometer.

Results: Cholesterol weakly bound to HA, followed by monoglyceride and palmitoyl palmitate < phosphatidyl choline, phosphatidic acid and sphingomyelin. The maximum amount of PL bound was 14 ± 1 µmoles inferring a 1 to 1 molar ratio of bound PL to HA dimer. Monoglyceride and palmitoyl palmitate required two to three times more lipid to achieve 100% bound HA compared to PL.

Conclusions: Physiological levels of HA, phosphatidyl choline and sphingomyelin would result in only 4% of the hydrophobic hydrogens of HA to be bound. HA-PL binding interactions could be important for therapeutic use of HA in eye drops in future studies to treat dry eye and to trap PL entering the VH to keep them from forming light scattering micelles. HA-lipid binding may also be relevant to the therapeutic effects of topical skin-care products. Both head group and hydrocarbon chain moieties influence HA-lipid interactions.

Keywords: Dye eye; Hyaluronan; Liquefaction; Nuclear magnetic resonance; Phospholipids; Vitreous humor.

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Conflict of interest statement

None of the authors have competing interests.

Figures

Fig. 1
Fig. 1
Hyaluronic acid polymeric structure. Protons in the hydrophobic face are in red
Fig. 2
Fig. 2
a A typical 1H-NMR spectrum of high molecular weight hyaluronan in D2O at 25 °C. U = d-glucuronic acid moiety, N = N-acetyl glucosamine moiety. b Effect of increasing dipalimitoyl phosphatidyl choline on the 1H-NMR spectra of hyaluronan. (Top to bottom) increasing concentrations of dipalimitoyl phosphatidyl choline as in Fig. 3a. The absolute intensities of the resonances of the HA–PL mixtures change from run to run due to instrumental tuning differences and the number of scans, so the data in Table 2 and in Fig. 3 were calculated and plotted relative to the intensity of the D2O resonance at 4.79 ppm
Fig. 3
Fig. 3
HA–lipid binding profiles. a Phospholipids with a choline headgroup (formula image) Phosphatidyl choline; (formula image) sphingomyelin. b (formula image) Cholesterol; (formula image) Phosphatidic acid. c Lipids found in the tear film lipid layer (formula image) the wax palmitoyl palmitate, (formula image) mono-glyceride. Lines are the linear regression fit
See this image and copyright information in PMC

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