(347a) Experimental and Computational Studies of Interfacial Interactions of Lignin Dimers with Lipid Bilayers

Experimental and Computational Studies of Interfacial
Interactions of Lignin Dimers with Lipid Bilayers

Mahsa Moradipour¹, Xinjie
Tong², Poorya Kamali³, Shardrack O. Asare³, Bert C. Lynn³,
Dorel Moldovan², Stephen E. Rankin¹, Barbara L. Knutson¹

¹Department of
Chemical Engineering and Materials Science, University of Kentucky

²Department of
Mechanical and Industrial Engineering, Louisiana State University

³Department of
Chemistry, University of Kentucky

Lignin is an organic substance present in cells,
cell walls, and between the cells of all vascular plants. While comprised of
only three monolignols (aromatic alcohols), it has a complex
structure variation in both sequence and types of bonds between monomers.  Due to the heterogeneity of the lignin
structure, the goal of deconstructing lignin to commercially viable small
molecules for use as chemicals or advanced materials has been elusive.  One potential application of lignin
derived molecules is antimicrobials or antifouling coatings.  This application is based on the known
inhibitory nature of deconstructed lignin components to microorganisms.

In this work, the interaction of three Beta-O-4 dimers of coniferyl alcohol (GG
lignin dimer) with synthetic lipid bilayers was studied: a commercially
available compound with no alcohol tail, the ÒnaturalÓ dimer containing a hydroxyl tail, and a benzyl-modified dimer. Small lignin molecules are thought to act as antimicrobials by interacting
with cell membranes, represented here as model phospholipid bilayers. A quartz
crystal microbalance (QCM) was used to study the amount of dimer uptake on
supported lipid bilayers and to compare effect of dimers on the properties of
the bilayer.  Corresponding
differential scanning calorimetry measurements (DSC) using lipid vesicles were
used to more directly study the change in bilayer phase behavior due to
incorporation of dimers into the bilayer. These measurements suggest that the
commercial GG and the benzyl-modified GG enter the hydrophobic region of the
bilayer, with similar partition coefficients (log K_m/w) of 2.9 and
3.0, respectively. However, significantly less natural dimer entered the lipid
bilayer (log K_m/w = 2.10).

Using
molecular dynamics simulations (MD) and free energy calculations, the interaction,
absorption, and partitioning behavior of lignin were investigated. The MD simulations show that aqueous
monomers and dimers absorb rapidly to the bilayer-water interface. The profile
of the free energy (PMF) curves indicate that the absorbed monolignols are
located close to the water lipid bilayer interface with very little affinity
for the bilayer interior. In contrast, some dimers are able
to penetrate significantly into the interior of the bilayer. In addition,
MD simulations of bilayers in the presence of higher concentration of dimers
(10%, 20%, and 40%) shows that they can have strong effect of bilayer structure
and permeation properties. The commercial and benzyl-modified dimers are both more
hydrophobic than the natural dimer and therefore have higher affinity for
bilayer interior and have a greater effect on its structure.  Overall, our results
indicate that minor differences in structure in lignin-based derivatives have a
significant impact on their interaction with lipid bilayers and that the techniques
used in this study will provide fundamental insight into interactions for
different lignin oligomers.  

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This project
is supported by NSF EPSCoR Track-2 RII, Award No.
OIA1632854, and National Science Foundation REU Program, University of Kentucky
(grant no. 1460486