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Amin Aghaei — 2012-13 Fellow

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  • Department: Civil & Environmental Engineering
  • Project Title: Multiscale Molecular Simulation of Biological Membranes for Targeted Drug-Delivery Applications
  • Amin Aghaei's Research Summary (PDF)

Medical treatment through drugs introduced into the human body are currently relatively crude in terms of targeting. Drugs are typically ingested orally or injected directly into the bloodstream. The chemicals disperse throughout the body rather than the specific site(s) requiring treatment, often leading to undesirable side-effects as well as lessening efficacy. In addition, dosages are often restricted to small quantities that must be administered at regular intervals of time, thereby placing restrictions on the lifestyle of the patient.

Targeted drug-delivery through engineered artificial biomimetic- and nano-structures can revolutionize health care by enabling targeted delivery to specific types of cells, as well as enabling the ingestion of large dosages that are released into “action” at a controlled rate. Recent demonstrations of targeted drug-delivery have shown the spectacular potential of the field. For instance, the Brinker group at Sandia / UNM have encapsulated therapeutic drugs in artificial biomimetic structures based on bacteriophage viruses. These viruses target a specific class of bacterial cells, thereby enabling precise control over the delivery of the therapeutic drugs.

Another example is the work of Professor Dai at Stanford University on cancer treatment by targeting carbon nanotubes. He coats the nanotubes with folic acid, which is vitamin B. Cancer cells have a lot of folic acid receptors, proteins on the outside of a cell that bind folic acid. So the cancer cells bind folic acid coated carbon nanotubes and then the nanotubes get inside the cancer cell. Once inside, an infrared laser is used to heat up the nanotubes. One property of carbon nanotubes is that they absorb infrared light and heat up. So, the cancer cells with the carbon nanotubes can be selectively heated up, while the normal cells don’t heat up at all. Only a few degrees of heat is enough to kill the cancer cells.

Achieving these possibilities requires fundamental advances in the theoretical understanding of how drugs and other bio-active molecules interact with both human cell membranes as well as artificial engineered drug-capsule walls. The aim of this research is to apply a unique multiscale molecular modeling technique to provide this theoretical understanding.

Fundamental advances in the understanding of the molecular mechanisms by which (i) potential drug encapsulation structures interact with the membranes of different types of cells; and (ii) drugs are transported to exit encapsulation membranes and enter cell membranes; will enable a guided strategy towards engineered drug-delivery that is both cell-specific and with controlled-release-rate. An essential difficulty in molecular modeling is that relevant system sizes of interest are very large. While molecular biology has developed accurate models of interactions between individual molecules that constitute the cell membrane (or the biomimetic drug capsule), the difficulty is that it is simply infeasible to solve these models on existing - or even conceived - computers. While accurate models of the individual interactions between the molecules are available, the cell membrane typically consists of well over a billion such molecules. However, multiscale methods are well-suited to such problems: near the region of activity, e.g. a drug molecule diffusing through the cell membrane, we can use molecular resolution to understand the critical features of drug/membrane interactions; away from the active region, we can coarse-grain to retain only the effective influence.

On the other hand, existing molecular multiscale methods are only suitable for engineering materials such as crystals. We will develop a unique molecular multiscale method – originally motived by complex nanostructures such as graphene monolayers and carbon nanotubes – that is suitable for the molecular structures that compose biological membranes. The research that is planned for the Dowd Fellowship is to apply the molecular multiscale method to the two questions noted above: (i) potential drug encapsulation structures interact with the membranes of different types of cells; and (ii) drugs are transported to exit encapsulation membranes and enter cell membranes. This will enable a guided strategy towards engineered drug-delivery that is both cell-specific and with controlled-release-rate.