Adsorption of galloyl catechin aggregates significantly modulates membrane mechanics in the absence of biochemical cues

Abstract

Physical interactions of four major green tea catechin derivatives with cell membrane models were systemically investigated. Catechins with the galloyl moiety caused the aggregation of small unilamellar vesicles and an increase in the surface pressure of lipid monolayers, while those without did not. Differential scanning calorimetry revealed that, in a low concentration regime (≤10 μM), catechin molecules are not significantly incorporated into the hydrophobic core of lipid membranes as substitutional impurities. Partition coefficient measurements revealed that the galloyl moiety of catechin and the cationic quaternary amine of lipids dominate the catechin-membrane interaction, which can be attributed to the combination of electrostatic and cation-π interactions. Finally, we shed light on the mechanical consequence of catechin-membrane interactions using the Fourier-transformation of the membrane fluctuation. Surprisingly, the incubation of cell-sized vesicles with 1 μM galloyl catechins, which is comparable to the level in human blood plasma after green tea consumption, significantly increased the bending stiffness of the membranes by a factor of more than 60, while those without the galloyl moiety had no detectable influence. Atomic force microscopy and circular dichroism spectroscopy suggest that the membrane stiffening is mainly attributed to the adsorption of galloyl catechin aggregates to the membrane surfaces. These results contribute to our understanding of the physical and thus the generic functions of green tea catechins in therapeutics, such as cancer prevention.

Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth

“…Interestingly, EGCG inhibited both IFNR/JAK2/STAT1 and EGFR/Akt signaling pathways, suggesting that EGCG inhibits IFN-γ-IFNR and EGF-EGFR activation by inhibiting ligand-receptor binding [ 11 ]. The results are consistent with a recent report that EGCG increased the bending stiffness of artificial lipid membranes by adsorption of galloyl catechin aggregates to the lipid membrane surface [ 20 ]. We also reported that stiffening of cancer cell membranes with EGCG correlates well with inhibition of EMT, motility, and metastasis in lung cancer cells and B16-F10 mouse melanoma cells [ 11 , 21 ].…”

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

“…The system reached its stability after 70 ns of MD simulation, as confirmed by RMSD values (Figure 5a), and showed a very similar stabilization In addition, the employement of EGCG concentrations above 0.5 mM had the effect to form large aggregates precipitating within the sample tube (data not shown). This appears to be in agreement with previous studies, in which emerged the propensity of EGCG to increase precipitation phenomena in the vesicle suspensions [48][49][50]; interestingly, the suspension mixed with C18-EGCG did not yield any precipitate.…”

Defining Lineage-Specific Membrane Fluidity Signatures that Regulate Adhesion Kinetics

“…Of note, polyphenols specifically reduced the adhesion of pluripotent cells but not other differentiated progeny, leading to an increased difference in adhesion kinetics ( Figure 4 D, left). The shape of F difference ( Figure 3 B) resembles that of the cholesterol-depleted membrane ( Figure S3 B, bottom), suggesting that polyphenols interact with membranes with fluidic lipids and cholesterol confirmed by model membrane experiments ( Figure 4 D, right) ( Hwang et al., 2003 , Karewicz et al., 2011 , Matsuzaki et al., 2017 , Neves et al., 2015 , Ogawa et al., 2016 , Sun et al., 2009 ).…”