Mechanics of Acute Leukemia

In diseases of the blood, changes in cell mechanical properties can have profound effects on the cells’ ability to flow normally through the vasculature, since increased stiffness impedes progress of cells through small capillaries.

In acute leukemia, immature blood cells of the myeloid or lymphoid lineages, called myeloblasts and lymphoblasts respectively, proliferate uncontrollably. Decreased deformability of these cells, as well as increased adhesion and transmigration, is thought to be linked to leukostasis, a poorly understood condition in which cells aggregate in the vasculature. This condition often results in intracranial hemorrhage and respiratory failure that rapidly leads to death, and current therapies based on removal of leukemia cells from the circulation have not proven to decrease mortality.

Better knowledge of biophysical changes in leukemia cells such as deformability is necessary for improved understanding of the disease. We are using atomic force microscopy to determine leukemia cell deformability and its impact on leukostasis. Our results have shown that the HL60 cells, a prototypical myeloid leukemia cell line, are significantly stiffer than Jurkat leukemia cells, a prototypical lymphoid leukemia cell line, and normal neutrophils. These results are consistent with clinical findings that myeloid leukemias result in leukostasis at higher incidences and at lower blood cell concentrations than lymphoid leukemias.

Giardia Attachment

The parasitic protozoan Giardia lamblia infests the mammalian gastrointestinal tract by attaching to the microvilli of small intestine epithelial cells. Giardia can remain in the lumen of the small intestine for weeks to years; infection is not always symptomatic but can cause severe malabsorptive diarrhea and contributes significantly to worldwide malnutrition levels.

Although the exact means of virulence is unknown, attachment is critical for resistance to intestinal peristaltic flow and thus virulence and attachment are linked. The ventral disk, a 7 um-diameter cytoskeletal structure occupying approximately 45% of the underside of the cell, is known to be involved in attachment and several mechanisms of attachment have been proposed in the literature. We are working to determine the exact mechanism Giardia uses for attachment and the role of the cytoskeleton in attachment. An understanding of how Giardia’s ventral disk generates attachment forces may provide both basic information about this unique cytoskeletal structure and directions for more specific methods of treating Giardia infections. This project is in collaboration with the W. Zacheus Cande Lab in the Department of Molecular Biology.