Structural and Dynamical Changes for different types of Lipid Bilayer by Different Length of Poly-L-Lysine: MD Simulations

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Poly-L-lysine (PLL), a cationic polypeptide, is toxic to a variety of cell types (Nano letters 8, 2008; Nano letters 5, 2005) and is also an ideal vector for gene delivery (Pharmaceutical Research 17, 2000;Molecular Therapy 6, 2002) by forming pore in cell membrane and letting small molecules passing through membrane with it. Molecular mechanisms for the controversial role of PLL in cell membrane remain unclear. We investigated the molecular interactions of poly(L-lysine) at two different lengths with three different types of lipid bilayer: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS) and mixed POPC and POPS bilayer with molecular dynamics (MD) simulations. One short PLL with more definite conformation and one relative long PLL with random conformation were used for this study. With the simulated systems reached dynamic equilibration, additional 200 ns production MD simulations were performed for each simulated systems. Results demonstrated that the interactions of different length of PLLs with the lipid bilayer directly affect the microscopic properties of a lipid bilayer: lipid head group area, tail order and bilayer thickness, further influencing the mesoscopic properties of the bilayer: electrostatic and mechanical properties of the bilayer. Results also showed that the different types of lipid bilayer can in turn influence the binding dynamics of PLLs with the lipid bilayer. The results will provide molecular insight for the experimental observations about the effect of PLL on cototoxicity and its role in gene delivery, further helping to optimize PLL length and lipid environment for best usage of PLL for its biological applications.