Spatiotemporal Dynamics of Endocytic Pathways Adapted by Small DNA Nanocages in Model Neuroblastoma Cell-Derived Differentiated Neurons

Abstract

Multiple endocytic pathways operate on the plasma membrane of cells at any moment with diverse but specific cellular functions. Knowledge of uptake of synthetic nanoparticles and ligands with respect to endocytic pathways is crucial to device the appropriate ligands for therapeutic delivery into differentiated neurons for targeting neuronal diseases. We herein explore the mechanisms of cellular uptake of 3D tetrahedral DNA nanocages at different stages of differentiating neurons. We monitored the uptake, kinetics, and dynamics of DNA cages of different geometries, and interestingly we find a specific pattern and adaptability of the uptake of DNA devices with respect to the geometry of the ligand and specific endocytic pathways. We find that tetrahedral DNA nanocages get endocytosed mostly via clathrin-mediated endocytosis in fully mature neurons. This endocytic uptake and intracellular choreography of DNA nanodevices will help us design the smartly targeted biotherapeutics for targeting neuronal disorders.

Water soluble, red emitting, carbon nanoparticles stimulate 3D cell invasion via clathrin-mediated endocytic uptake

“…Lactose is known to compete with extracellular Gal3 for binding to specific β-galactosides on the plasma membrane receptors and, therefore, used to inhibit the uptake of extracellular Gal3. 25 It was observed that the uptake of Gal3 was significantly decreased when inhibited by lactose (CIE blocker), whereas CNPs uptake was marginally affected in cells ( Figure 7c, d ). However, on inhibition via dynasore, the uptake of Gal3 was reduced only marginally.…”

Designer Dna Hydrogels to Stimulate 3d Cell Invasion by Enhanced Receptor Expression and Membrane Endocytosis

“…Transferrin (Tf) and galectin-3 (Gal3) are classical ligands used to study the clathrin-mediated and clathrin-independent pathways, respectively. 28 Cholera toxin B-subunit (CTxB) binds to lipid GM1 on the plasma membrane and builds tubular endocytic tubules which are scissioned by cellular machinery like dynamin or actin or endophilin. These internalized vesicles then mature into early endosomes from where CTxB retrogradely transports to endoplasmic reticulum via plasma membrane and Golgi bodies 29 We compared the change in cellular internalized fractions of all the above ligands in RPE1 cells seeded over DNA HGX coated and an uncoated glass coverslip.…”

Designer DNA Hydrogels Stimulate 3D Cell Invasion by Enhanced Receptor Expression and Membrane Endocytosis

“…Transferrin (Tf) and galectin-3 (Gal3) are classical ligands used to study the clathrin-mediated and clathrin-independent pathways, respectively. 36 Cholera toxin B-subunit (CTxB) binds to lipid GM1 on the plasma membrane and builds tubular endocytic tubules that are scissioned by cellular machinery like dynamin or actin or endophilin. These internalized vesicles then mature into early endosomes from where CTxB retrogradely transports to endoplasmic reticulum via plasma membrane and Golgi bodies.…”