During the last decade, nanomaterials (e.g., nanoparticles, carbon nanotubes, graphene) have received intense global interest due to their wide ranging applications in cosmetics, energy storage, automotive parts, boat hulls, sporting goods, water filters, thin-film electronics, coatings, actuators and electromagnetic shields. In biomedical science and technology, major advances have been made in the applications of nanoparticles in cancer targeting, drug delivery, and enhanced bioimaging. The timeliness of this project can be judged based on the urgent societal needs to understand both beneficial and hazardous effects of nanotechnology which have resulted in the release of hundreds of thousands of tons of nanomaterials into the environment each year. Over the past 5 years, the Principle Investigator (PI) and his team have performed cutting edge research aiming to address the current lack of understanding on the roles of elasticity and aspect ratio of nanoparticles in the cell uptake of carbon nanotubes and other potentially toxic nanoparticles. This research has produced the following major findings.

Cell uptake of elastic nanoparticles. In the field of cell interaction with viral nanoparticles, an intriguing finding has been that murine leukemia virus (MLV) and human immunodeficiency virus (HIV) regulate their mechanical properties at different stages of their life cycle through internal morphological reorganization. So far little is known about the biophysical mechanisms underlying this behavior. The PI and his team developed the first theoretical model on cellular uptake of elastic nanoparticles (Fig. 1). He showed that the mode of interaction between cell membrane and a nanoparticle is strongly affected by particle stiffness. This theory provided an explanation of the stiffness regulation behaviors of MLV and HIV viruses.  

Cell uptake of high aspect ratio nanomaterials. Materials with high aspect ratio, such as carbon nanotubes and asbestos fibres, have been shown to cause length-dependent toxicity in certain cells because these long materials prevent complete ingestion and this frustrates the cell The PI and his team discovered a fundamental pathway for one-dimensional nanomaterials to enter cells in a nearly perpendicular entry mode (Fig. 2). This finding provided a fundamental understanding of how cells interact with high aspect ratio nanomaterials.

Cell penetration by two-dimensional nanomaterials. Understanding and controlling the interaction of two dimensional synthetic materials (e.g., graphene) with cells is key to the development of biomedical applications of nanotechnology. The PI and his team discovered that graphene microsheets (with lateral dimensions on the order of tens of micrometers) can spontaneously pierce into a cell membrane at corners or asperities (Fig. 3).

 Cell uptake of ligand-coated nanoparticles. The cell uptake rate of nanoparticles coated with mixed hydrophilic/hydrophobic ligands is known to be strongly influenced by the ligand pattern on the nanoparticle surface. The PI and his team conducted the first theoretical analysis on cell uptake of nanoparticles coated with different patterns of hydrophilic/hydrophobic ligands (Fig. 4). The findings not only explained the experimental observations but also provided useful guidelines for the molecular design of patterned nanoparticles for controllable cell penetrability.

The above findings not only significantly advance the scientific understanding of mechanisms by which nanomaterials enter human and animal cells, an issue of tremendous societal concern regarding both beneficial and potential hazardous effects of nanotechnology on health and environment, but also provide insights or guidelines for the development of efficient gene and drug targeting and delivery systems in bio...

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