One of the leading epidemics of modern society – the HIV virus and AIDS – is under the microscope at the UH Cullen College of Engineering.
“This virus deserves both the fear and the scientific scrutiny that has been showered on it,” said mechanical engineering Ph.D. student Himani Agrawal, one of the Cullen College engineers who recently wrote a paper for the journal Scientific Reports, published by the prestigious Nature group, illustrating how the research team used atomistic simulations and mathematical models to explain past experiments and to precisely elucidate the mechanism by which the HIV virus softens the cell to infect it.
Considerable work has been done on how the HIV virus infects a healthy host cell. More recently, researchers have found that one of the ways the virus enters the cell is by reducing its mechanical strength and digging a hole in it.
Breaking down the cell
Every cell is surrounded by a thin skin called the membrane. The inside of the cell contains all the life-sustaining bio-goodness that we need. Think of the cell as a sac of liquid-ish jelly with the membrane as the gatekeeper (much like skin) that allows only the “right” things to go in and out.
Now, imagine a drop of water on a piece of notebook paper. The affected area will lose its mechanical strength, or “soften,” making it easy for something to poke a hole and enter through the paper. Similarly, one of the key steps in the HIV-infection process is the fusion of the virus membrane to the target cell membrane.
“Past experimental evidence suggests that the fusion is preceded by considerable elastic softening of the cell membranes due to the insertion of fusion peptide in the membrane,” said Agrawal. “But what are the mechanisms underpinning the elastic softening of the membrane upon peptide insertion?”
One of the key mysteries that this research group resolved is to explain why the insertion of a relatively rigid object (HIV fusion peptide) in a soft mushy membrane does not lead to hardening but to softening.
To explain this, Agrawal and fellow student, Matthew Zelisko, carried out atomistic simulations to investigate peptide-membrane interactions. The resolution of this paradox is the key theme of the published paper.
At this point, it’s hard to say what the consequences of this study might be. The focus of the work is on fundamental science, but further experimental and theoretical work on the disruption of the elastic softening due to HIV infection is a possible direction of research to better understand this and other such infection processes.
The study was conducted under the guidance of Agrawal’s adviser, Pradeep Sharma, M.D. Anderson Professor and chair of the department of mechanical engineering and collaborator, Liping Liu, associate professor of mathematics, mechanical and aerospace engineering at Rutgers University.
The research published in Scientific Reports was funded by the M.D. Anderson Professorship and grants from the National Science Foundation (NSF).