ApoE binding
to LNP as measured by LNP immobilized particles on
a QCM-D sensor. The raw frequency shift for overtone 5, 7, and 9 is
reported as a function of ApoE concentration (A). The frequency shift
has been offset by the equilibrium value obtained after LNP injection/rinsing.
The overlap for all overtones suggests that the ApoE is a rigid film
adsorbed on the LNP (no change in dissipation occurs). Note that a
negative change in frequency is related to an increase in adsorbed
wet mass. The number of ApoE molecules per LNP as a function of ApoE
concentration is calculated assuming hexagonal (gray squares) and
random (black circles) packing by using the Sauerbrey equation (B).
Transition of free ApoE44 (PDB ID: 2l7b) into proposed hairpin-like
configuration43 adapted to fit on an 80
nm diameter LNP (green). Domains bound to the LNP surface are shown
in red with hydrophobic leucines and isoleucines shown as sticks (C).
The illustration was prepared using the PyMOL Molecular Graphics System,
version 2.0, Schrödinger, LLC.