Host cell lipid bilayer

The host cell lipid bilayer is the fundamental structural barrier and functional interface for the delivery of vaccine lipid nanoparticles (LNPs). Composed primarily of phospholipids, cholesterol, and integral proteins, the bilayer regulates the entry of LNPs through mechanisms such as receptor-mediated endocytosis and macropinocytosis (Schoenmaker et al., 2021). The interaction between the LNP and the host membrane is highly dependent on the lipid composition of both entities, particularly the presence of ionizable lipids that respond to pH changes within the endocytic pathway. Successful delivery requires the LNP to destabilize the endosomal lipid bilayer, a process known as endosomal escape, to release nucleic acid cargo like mRNA into the cytoplasm for translation (Sahay et al., 2013). Beyond its role as a barrier, the host membrane's response to LNP interaction can influence cellular signaling and potential toxicological outcomes, making it a critical focus for optimizing nanomedicine efficacy and safety (Cullis & Hope, 2017).

Other names

Plasma membraneEndosomal membraneCell membraneBiological membraneCytoplasmic membrane

Lipid nanoparticles (LNPs) interact with the host cell lipid bilayer to facilitate intracellular delivery. The process typically involves the adsorption of host proteins like Apolipoprotein E (ApoE) to the LNP, which then binds to receptors on the plasma membrane to trigger endocytosis (Akinc et al., 2010). Within the acidic environment of the endosome, ionizable lipids in the LNP become protonated and interact with the anionic lipids of the host endosomal membrane, causing a transition from a bilayer to a hexagonal HII phase that disrupts the membrane and releases the cargo into the cytosol (Cullis & Hope, 2017; Sahay et al., 2013).