Lin Han, PhD,
an associate professor in the School of Biomedical Engineering, Science and Health Systems, has received a CAREER award from the National Science Foundation (NSF) to study fibrous tissues at the nanoscale, advancing the treatment and understanding of cartilage diseases, such as osteoarthritis.
The NSF’s CAREER program offers the foundation’s most prestigious awards in support of early-career, non-tenured faculty who have the potential to serve as academic role models in research and education. CAREER projects should “build a firm foundation for a lifetime of leadership in integrating education and research,” according to the NSF.
Fibrosis — which can occur in the lungs, liver, joints, and many other tissues in the body — is an exaggerated wound healing response. While trying to repair itself after an injury, the body forms layers of connective tissue, which can interfere or inhibit the normal architecture of the underlying organ or tissue.
Han is studying this process — the changing properties of collagen fibers — at the nanoscale, zooming into the soft coatings of molecules that surround cartilage cells.
“If you put a cell in a very stiff, fibrotic environment, the cell will freak out and make more fibers. It becomes an irreversible, bad loop – your body makes more fibers, and there is more freaking out. That’s what leads to disease,” Han said.
A nanoscale view of the unique structure and composition of an adult mouse's murine meniscus pericellular matrix (PCM). Left: The PCM has random, porous collagen fibril architecture, which is distinct from the highly aligned and densely packed collagen fibers in the bulk matrix. Right: The PCM shows localization of sulfated sugars (glycosaminoglycans, red), as well as proteoglycans, such as perlecan and aggrecan (green, blue stains for cell nucleus).
The NSF funding will allow Han’s lab to generate new knowledge about the biomechanics of the pericellular matrix (PCM) — a thin coat that surrounds fibrous tissue cells. Recent studies have suggested that this “coat” could play a pivotal role in regulating fibrocartilage, which can be found, for example, in the knee joint meniscus.
To better understand the unique composition and mechanical feature of the PCM, Han, along with PhD candidate Chao Wang, plan to study mice with collagen genes that have been inactivated or “knocked out.” Han and Wang will use their expertise in atomic force microscopy to see how the activity of the cell changes without these genes, mimicking what goes awry in fibrotic tissue.
“We use the tip of this microscopy tool to poke specific regions, and with the model, we will be able to calculate, what is the local stiffnesss of the tissue at very immediate contact with the cell?” Han said.
Han says this research will advance research into problems like incurable, chronic knee pain, which afflicts millions every year. By studying the role that this unique coating plays in preventing fibrosis, clinicians may one day be able to prevent and control the fibrotic process in patients.