A3 Cellular Uptake and Translocation

Topic

The interaction of this nanoparticle with the cell membrane does not depend on its mass—unlike the assumption made in conventional chemical toxicology for most substances—but rather on its size and surface energy. According to Deserno's model, these two properties—size and surface energy—determine the membrane-wrapping energy the cell membrane must expend to completely engulf the nanoparticle. Consequently, if the nanoparticle is larger or has higher surface energy, the required membrane-wrapping energy also increases.

However, this membrane-wrapping energy cannot indefinitely exceed the energy the cell membrane itself has available to deform around the nanoparticle; this available wrapping energy thus defines a critical uptake radius for the nanoparticle—the maximum size it can have while the cell membrane still possesses enough energy to fully engulf it. A higher level of available wrapping energy in the cell membrane results in a larger critical uptake radius, thereby allowing for the engulfment of larger nanoparticles.

Therefore, based on the nanoparticle's size and surface energy, reaching—but not exceeding—this critical uptake radius is the condition that enables the nanoparticle's efficient internalization via endocytosis: a nanoparticle with a size and surface energy below this critical radius (allowing the cell membrane to fully engulf it) is internalized efficiently, whereas a nanoparticle exceeding this radius remains beyond the reach of this internalization pathway. The fact that this condition depends—in this way—on the size and surface energy of the nanoparticle, rather than its mass, means that two nanoparticles of the same mass but different sizes or surface energies can have completely different fates regarding the same cell membrane; furthermore, the fact that this surface energy can be deliberately modified—according to another model in this set—through surface functionalization means that such functionalization ultimately determines the nanoparticle's biocompatibility with respect to this condition of efficient internalization.

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