Effects of Nanoparticle Morphology and Acyl Chain Length on Spontaneous Lipid Transfer Rates

Abstract

We report on studies of lipid transfer rates between different morphology nanoparticles and lipids with different length acyl chains. The lipid transfer rate of dimyristoylphosphatidylcholine (di-C14, DMPC) in discoidal "bicelles" (0.156 h(-1)) is 2 orders of magnitude greater than that of DMPC vesicles (ULVs) (1.1 × 10(-3) h(-1)). For both bicellar and ULV morphologies, increasing the acyl chain length by two carbons [going from di-C14 DMPC to di-C16, dipalmitoylphosphatidylcholine (DPPC)] causes lipid transfer rates to decrease by more than 2 orders of magnitude. Results from small angle neutron scattering (SANS), differential scanning calorimetry (DSC), and fluorescence correlation spectroscopy (FCS) are in good agreement. The present studies highlight the importance of lipid dynamic processes taking place in different morphology biomimetic membranes.

Fast Collisional Lipid Transfer Among Polymer-Bounded Nanodiscs

“…Even faster kinetics have been reported for TX-100 micelles ( k obs  = 1.5 × 10 5  s −1 ). By contrast, DMPC exchange among gel-phase bicelles35 is slower than lipid transfer in any of the above fluid-phase systems.…”

Breakage of Hydrophobic Contacts Limits the Rate of Passive Lipid Exchange Between Membranes

“…[8][9][10] Previous computational work [11][12][13][14][15] on lipid transport has presumed that a lipid's displacement normal to the membrane is the reaction coordinate ( Figure 1A) and has yielded results in conflict with experimental findings. [16][17][18][19] Here we show that the reaction coordinate for passive lipid exchange is indeed more subtle than a simple distance measurement. The reaction coordinate characterizes the creation (or disruption) of a locally hydrophobic environment around the incoming (or outgoing) lipid ( Figure 1B).…”

“…Based on experimentally measured activation energies, calculated activation free energies for lipid exchange exceed free energies for transferring a lipid from water to a membrane, indicating that there is a barrier for lipid desorption and insertion. [16][17][18][19] At this barrier, the desorbing lipid is hypothesized to only have the terminal carbons of its tails left within the membrane. 16,27 Thus, the activation free energy required to form the transition state has been attributed to the creation of a cavity in the membrane due to partial removal of a lipid and another cavity in the solvent to accommodate that lipid.…”

“…[11][12][13][14][15] These free energy profiles lack a barrier for insertion, [11][12][13][14][15] seemingly in conflict with experimental results. [16][17][18][19] If the COM displacement is not the reaction coordinate for lipid exchange, the kinetically relevant barrier may not be resolved in these free energy profiles; instead, a barrier may exist along a different degree of freedom that is the reaction coordinate. Consistent with this idea, Vermaas and Tajkhorshid's MD study of lipid insertion indicated that the COM displacement is not sufficient to fully describe the microscopic dynamics of lipid insertion.…”

“…32 Our Approach. The discrepancy between experimental [16][17][18][19] and computational [11][12][13][14][15] reports about a barrier for lipid exchange, together with the evidence suggesting that the lipid's COM displacement is a poor reaction coordinate from a MD study of lipid insertion 32 prompt two questions: (1) What is the reaction coordinate for lipid exchange? (2) What, if any, activation free energy barrier impedes the process of lipid insertion?…”