Cholate-conjugated cationic polymers for regulation of actin dynamics.

Cytoskeletal movement is a compulsory necessity for proper cell functioning and is largely controlled by actin filament dynamics. The actin dynamics can be fine-tuned by various natural and artificial materials including cationic proteins, polymers, liposomes, and lipids, although most of the synthetic substrates have toxicity issues. Herein, we show actin nucleation and stabilization with a synthetic family of cholic acid (CA)-conjugated cationic macromolecules. Architectural conjugation of CA is designed by attaching it to the polymer chain end, as well as to the side chain of the polymer. The side-chain cholate content is also varied in the copolymer, which results in self-aggregation in aqueous media above a certain critical aggregation concentration (CAC). Below the CAC, the in vitro actin dynamics modulation behaviour is studied using a pyrene actin fluorescence assay, actin co-sedimentation assay, dynamic light scattering (DLS), and transmission electron microscopy (TEM). These polymers are nontoxic to HeLa cells, and the 2% cholate conjugated cationic copolymer showed maximum enhancement of G-actin nucleation, as well as F-actin stabilization. We further develop a theoretical model to elucidate the underlying dynamics of the actin polymerization process under the influence of cationic copolymers with cholate pendants. Finally, we proposed macromolecular self-aggregation as a unique tool for modulating actin dynamics, as revealed from the experimental findings and theoretical modelling.

Enzymatic synthesis of lipophilic lutein-PUFA esters and assessment of their stabilization potential in EPA-DHA rich fish oil matrix.

The objective of the present study was to synthesize ω-3 polyunsaturated fatty acid esters of lutein and to evaluate if esterification can stabilize the both bioactive molecules. Both ω-3 polyunsaturated fatty acid and lutein are prone towards auto-oxidation in their free form. Free lutein extracted from the marigold petals was enzymatically esterified using Candida antarctica NS435 Lipase B, with the ω-3 long-chain polyunsaturated fatty acids. The lutein esters were purified, characterized and finally assessed for their protective role against oxidative degradation in bulk fish oil matrix. The antioxidative effect of these esters was compared with commercial antioxidants of natural origin, i.e., α-tocopherol and a synthetic antioxidant, i.e., tert-butylhydroquinone, at a dosage of 200 mg/L. Both free lutein and lutein-polyunsaturated fatty acid ester had significantly promoted the oxidative stability of bulk fish oil. But based on dose-response relationship, lutein-polyunsaturated fatty acid ester was found to be more efficient than free lutein, in protecting fish oil from secondary oxidation, thereby augmenting their shelf life. Given the high nutraceutical value, potent antioxidative potential and organic origin, it is only relevant to incorporate lutein esters as natural preservative and stabilizers in edible oils.