A closed mouth
Deborah Leckband: Sticky Situations
Where, when, why and how do molecules say to one another, “Hey, let’s stick together?” That’s the fundamental question that Deborah Leckband, Milner T. Reid Professor of Chemical Sciences, ponders.
Leckband first became interested in adhesion on surfaces where it causes problems: ships’ bottoms fouled with algae, contact lenses coated in protein deposits, implanted devices coated in molecules that trigger an immune response. What is the chemical basis of adhesion and how can we control it, Leckband wanted to know.
But pretty quickly Leckband realized that the field of cell surface adhesion is broadly fundamental and affects many different aspects of biology. For example, she has investigated issues in wound healing, drug delivery, and pathogen recognition. Because of the wide-ranging applicability of her field, she has appointments in many places beyond her home of Chemical and Biomolecular Engineering, including biochemistry, nanotechnology, and the Beckman Institute. She is also director of the campus-wide graduate bioengineering program.
Leckband started out to understand the chemical basis of non-specific adhesion and how to manipulate it. She helped develop polymer coatings on implants and on drug carriers, to improve their effectiveness.
From there Leckband became interested in situations where adhesion is desirable. How do proteins intentionally promote or prevent natural biological adhesion? In the case of implants, for example, are there material properties that might promote adhesion and thus encourage tissue to grow around an implanted scaffold?
“This gets us into the biological aspects of our work in that we are looking at how adhesive contacts between cell surface receptors and these materials influence how cells respond to those materials through biophysical signaling pathways,” says Leckband.
This work led Leckband to investigate how cells send and gather information using mechanical signals, or force.
“For years researchers have focused on how soluble chemical signals and electrical signals influence cell and tissue functions, but in the last decade or so people started to realize mechanical signals are probably just as important,” she says.
Working with Ning Wang, professor of mechanical science and engineering, Leckband’s team discovered a group of proteins at the contacts between cells — already known to hold cells together in tissues — that are also force sensors.
“Proteins are not only important in mediating the physical gluing of the cells to the surface, but also are transmitting biochemical and mechanical signals to the cell that tells the cell how to function in that environment,” says Leckband, of that finding.
Working with Hyunjoon Kong, also a professor in ChBE, Leckband is investigating how the discoveries she made with Wang might influence stem cell differentiation, and thus tissue formation, as well as neural networks.
In related work, Leckband is studying ventilator-induced lung disease in collaboration with a pulmonary medicine group in Chicago. This mechanically induced pathology occurs when normal forces exerted on the lung tissue by a ventilator cause fluid to leak into the air spaces in the lungs.
Leckband’s group has built devices that enable them to monitor cell behavior when the lung tissue is subjected to mechanical perturbation. They then use quantitative methods to analyze the results. This approach leads to better understanding of the processes involved.
These techniques help Leckband’s group understand the basics of lung injury as well as the influence of genetic variation on susceptibility to lung injury. These same tools help them quantify the effects of protective drugs to understand how different drugs may either protect against injury or promote repair after the fact.
In another medical example, Leckband worked with a group in London to understand how the structure of adhesion proteins on dendritic cells within the immune system enable the dendritic cells to recognize, bind to and then destroy pathogens. Sometimes pathogens, such as HIV, take advantage of these proteins to attack and destroy the immune system. Leckband’s group identified certain features of the adhesion molecules on the dendritic cells that might be important for their ability to recognize both viral and microbial pathogens.
Although she doesn’t explicitly espouse it, Leckband personifies the “Lean In” philosophy that Sheryl Sandberg of Facebook has made a household term. In a field in which women are scarce, Leckband, a woman who measures her words carefully and precisely, makes sure to always take her place at the table, to lean in.
“My philosophy has always been that if you act like you belong there, then you will. People will accept you,” says Leckband, one of two female faculty members in ChBE.
Leckband’s interest in translational work is also reflected in her teaching. This past fall, for example, she taught an upper-level seminar on techniques in biotechnology. The course demonstrated how biological information is used to generate new technologies but also emphasized meeting design targets and understanding how to make a good product.
She had the students analyze different products, such as a pregnancy test, and explain how the technology was developed to achieve the goals. The students had to identify the design goals. In the case of a pregnancy test those goals would include needing to be fast and easy to use. Students then determined whether and how the product met those goals.
“Engineering is more than coming up with a cool discovery,” says Leckband. “It’s also about how to get the product to market.”
The kinds of problems Leckband’s lab works on concern these precise goals.
“We are always asking, ‘How can this information be used to make a better product?’”