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High resolution differential scanning calorimetry (DSC) and molecular dynamics (MD) simulations were used to investigate the effect of three lignin dimers on the gel to fluid phase transition in DPPC lipid bilayers. The goal of this research is to begin to understand the partitioning of model lignin dimers into lipid bilayers and its effects on the gel to fluid transition temperature (Tm). The long-term objective is to establish structure–function relationships for well-defined lignin derivatives at biologically relevant surfaces. This work uses a newly synthesized guiacylglycerol guaiacol ester with a hydroxypropenyl (HOC3H4−) group resembling natural lignin (GG dimer), compared with a truncated GG dimer without the HOC3H4– and benzyl-modified GG dimers. The DSC results show that the dimer most like natural lignin (with a hydroxypropenyl tail) has log K= 2.72 ± 0.05, and MD simulations show that it associates with the headgroups of the lipid but does not penetrate strongly into the interior of the bilayer. Therefore, this dimer has little effect on the Tmvalue. In contrast, the truncated dimer, which has been used as a representative GG dimer in prior studies, partitions into the bilayer, as seen in MD simulations, and shifts Tmbecause of its increased lipophilicity (DSC log K= 3.45 ± 0.20). Similarly, modification of the natural GG dimer by benzylation of the phenol makes it lipophilic (DSC log K= 3.38 ± 0.28), causing it to partition into the bilayer, as seen in MD simulations and shift Tm. In MD, we capture the transition from gel to fluid phase by defining and analyzing a normalized deuterium order parameter averaged over all carbon atoms located in the middle of the lipid tails. In this way, the phase transition can be clearly observed and, importantly, MD results show the same trend of transition temperature shifts as the DSC results. Furthermore, we compare partition coefficients estimated from free energy profiles calculated in MD to those obtained from experiment and they are in qualitative agreement. The success at predicting the structural effects of lignin dimers on lipid bilayers suggests that MD simulations can be used in the future to screen the interactions of lignin oligomers and their derivatives with lipid bilayers. more...