HDL (High Density Lipoprotein) is the smallest of the five major groups of lipoproteins which play an essential role in plasma lipid transport. HDL transports cholesterol from blood vessels to liver for excretion. As this “reverse cholesterol transport” decreases the risk of cardiovascular disease, HDL acting as a carrier of cholesterol is often called “good cholesterol”. Electrostatic properties of small particles like HDL affect their stability and interactions with for example lipid membranes. In this project the goal was to use molecular dynamics simulation to measure the zeta-potential of HDL particle. I also wrote my bachelor’s thesis about this topic.
Charged particles, like HDL, affect the ion distribution around them. The concentration of counter ions is higher close to the surface, and an electrical double layer is formed around the particle. The double layer consists of two parts: an inner region where ions are tightly bound to the particle, and an outer region where ions are less firmly attached. The boundary between these regions is called the slipping plane, and the electrostatic potential on this plane is called the zeta potential. The value of zeta potential is related to the stability of a colloidal dispersion. If zeta potential is high, particles repel each other and they will not coagulate. The value of zeta potential can be determined experimentally by measuring electrophoretic mobility. The experimentally measured zeta potential of HDL is about 12.4 mV .
From molecular dynamics simulations it is easy (in theory) to calculate electrostatic potentials, as the exact positions and charges of all atoms are known. Heikkilä et al have determined the zeta potential for a gold nano particle , but using the same method for HDL is a bit trickier. HDL is bigger and more complex, and the total charge is lower. At least one microsecond long simulations are needed to get enough statistics, and still the results might depend on the initial structure protein around HDL.
Also determining the slipping plane is problematic, because the surface of the particle is penetrable by water and irregular in shape. Heikkilä et al defined slipping plane by fitting a Debye-Hückel equation to the radial distribution of counter ions around the particle. Using this method gives 6.5 nm for the radius of slipping plane. The potential at that radius would be about -2 mV.
- Zhang, Wen-Li, et al. “Nanostructured lipid carriers constituted from high-density lipoprotein components for delivery of a lipophilic cardiovascular drug.” International journal of pharmaceutics 391.1 (2010): 313-321.
- Heikkilä, Elena, et al. “Atomistic simulations of functional Au144(SR)60 gold nanoparticles in aqueous environment.” The Journal of Physical Chemistry C 116.17 (2012): 9805-9815.