Shuguang Zhang’s move from exploring genes –– a traditional focus for someone with a molecular biology Ph.D. –– to the new and chancier field of designed biological materials was triggered by an experience in Alexander Rich’s lab at MIT 12 years ago.
Zhang was probing a yeast protein that binds to DNA. A tiny stretch of the protein, he found, had an unusual, and intriguing, molecular structure. Zhang, then a postdoctoral fellow, asked brain and cognitive sciences grad student Todd Holmes to help him explore the segment, known generically as a peptide.
“One day Todd called. ‘Something strange is going on,’ he said,” recalls Zhang, now associate director of MIT’s Center for Biomedical Engineering. “I went over and looked through the microscope. We had put variants of these peptides in different conditions in a dozen petri dishes. In two of the dishes, there was a membrane over the surface that looked like Saran Wrap.”
It took Zhang a year-plus to figure out what that odd substance was: a biological material that had undergone molecular selfassembly to form what’s now called a hydrogel matrix.
Self-assembly happens all the time in nature. Spider webs and hair are examples of structures created by fibrous proteins interwoven with each other. Nature also demonstrates self-assembly’s powers: a silk fiber more than a mile long can come together in the fiber-forming glands of a silkworm in a mere two to three days.
Zhang recognized that self-assembly in the lab could lead to “nano-” structures –– structures with dimensions measured in billionths of a meter –– and maybe molecular machines, too. But it took a decade of experimenting with materials and techniques for potential uses to come into focus.
While the self-assembling peptide materials incorporate amino acids –– the building blocks of proteins –– they’re mostly water (hence the name “hydrogel.”) They can selfassemble into a range of shapes, from nanotubes to fine 3-D nanofiber webs. Their dimensions are tiny: a tubule is 30 to 50 nanometers wide, or about a thousandth the diameter of a human hair. And, they’re biodegradable.
What do such traits make them useful for? One application is as scaffolds for new tissues. “The dimensions of the individual strands in a hydrogel web are the same as the components of the matrix that surrounds most cells,” explains Zhang.
MIT’s Alan Grodzinsky has already grown cartilage cells on hydrogels. And Zhang and Holmes –– the latter now on New York University’s faculty –– have shown that the nervous-system cells called neurons readily grow new extensions on hydrogel scaffolds, which may point to a role for such scaffolds in treating conditions like stroke.
Vision can be eliminated by a stroke. Gerald Schneider, an MIT professor of brain and cognitive sciences, has restored sight to lab rodents by implanting nerve fibers from elsewhere in their bodies into their brains. But hydrogel-based “bridges” could work better yet.
Hydrogels, notes Rutledge Ellis-Behnke, a grad student in Schneider’s lab, can harbor extremely useful “passengers” –– the cell stimulators called growth factors, for example.
“From our work with transplanted nerve fibers, we already have a benchmark for the restoration of visual function,” says Ellis-Behnke. “Now, we can see how hydrogels match up against that.”
Although the effort’s new, one intriguing long-term possibility would be to simply inject appropriately treated hydrogels into a stroke victim’s brain. “Remember,” notes Zhang, “these hydrogels are mostly water. You can administer them just as you would a drug.”