The Image: "Two Dimensional Protein Crystal Structure Imaged by Hi-Res Atomic Force Microscopy"
The image depicts the two dimensional crystal formation of the protein annexin A5 (AnxA5) on a planar phospholipid layer. It was acquired using an imaging technique called atomic force microscopy (AFM), where a sharp probe attached to the end of a cantilever is scanned across the surface of a sample, generating a surface profile. This is a very tactile-based imaging system, somewhat akin to the interpretation of a braille message using the fingertips.
The image is from research we are performing in collaboration with Dr. Jacob Rand at Cornell Medical School to try and understand the etiology of the antiphospholipid syndrome (APS), which is a human thrombotic disorder (think: blood clots). We know that AnxA5 forms a protective, anti-coagulant shield on the surface of placental trophoblastic cells and endothelial cells lining the blood vessels. The hypothesis we are testing postulates that APS is caused by an antibody-mediated disruption of this two dimensional AnxA5 protective shield on the surface of cells, resulting in the exposure of underlying phospholipid molecules which serve as scaffolds for the binding of proteins involved in the clotting cascade. To create a simple model system to initially test this hypothesis, we allowed two dimensional AnxA5 crystals to form on a simple planar lipid layer (as shown in the image), and then treated this complex with antibodies from patients with APS. The AFM results definitively showed that the patient-derived antibodies did indeed disrupt the two dimensional crystal shield on the lipid, confirming our hypothesis in a model cell-free system. Currently, we are extending these studies to cell-based systems, as well as investigating molecules which may be employed to pharmacologically repair the crystal structure defects. Interestingly, the high resolution imaging capabilities of AFM using samples unfixed in fluid proved to be the only experimental modality available to allow us to directly test our hypothesis.
I knew I wanted to be a scientist since elementary school. I was a product of the “space race” of the 1960s, and though I was originally interested in astronomy, settled on biology after taking some classes in high school. I went on to obtain a B.S. in Biological Sciences, M.S. in Anatomy & Physiology, and a Ph.D in Cell Biology. I became most interested in microscopy while working in an electron microscopy laboratory as an undergraduate student. This in turn led to my widespread interest in all aspects of microscopy and imaging sciences, such that I now direct the Microscopy Imaging Center in the College of Medicine at the University of Vermont. Although I now consider myself an “imaging” person, I have no artistic abilities (cannot even draw a good stick figure), but I appreciate art and always look for interesting patterns and structures in my images.
Are you currently working in a lab setting or pursuing work in art + science?
I have been at the University of Vermont for 27 years, and am currently a Professor in the Department of Pathology and Laboratory Medicine, and Director of the Microscopy Imaging Center in the College of Medicine.
Did you ever have an “aha!” moment when you knew you wanted to pursue a career in science? Did you intend for this path to include art + design?
As mentioned above, I knew I wanted to be a scientist since elementary school days. I was curious and interested in science as a child, but I guess my “aha!” moment came when in sixth grade I was asked to develop a theme for an upcoming parent/teacher conference. With the recent success of the Apollo 11 mission to the moon, I chose space flight as the topic. I wrote to NASA to query about this topic, and they proceeded to send me boxes full of pamphlets, posters, photographs, booklets, etc. It was incredibly exciting to decorate the school cafeteria with all of this paraphernalia, solidifying my desire to become a scientist. Again, given my artistic limitations, art and design never entered my conscious thinking process.
Images & image description courtesy of Doug Taatjes, PhD.