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Our laboratory is developing applications of molecular mechanics to the challenges
of targeted drug and gene delivery. To increase specificity and reduce toxic
side effects, we are incorporating leukocyte adhesion receptors into liposomes
and polymeric microparticles containing encapsulated therapeutics to target
defective cells with high specificity. To this end, we are using a mutagenesis
approach coupled with biophysical analysis of mechanically stressed bonds to
identify the controlling features of adhesion receptors that permit binding
in the presence of fluid shear forces.
Additionally, we have developed several model flow systems to examine the dynamics
of platelet-leukocyte-vessel wall interactions that take place during the acute
phases of an inflammatory challenge or the formation of blood clots on the vessel
wall. Common to interactions between platelets, leukocytes, and the vessel wall
is the involvement of a family of receptors called selectins that support transient
adhesions in which leukocytes and platelets roll along the vessel wall in shear
flow. These studies have significance for the understanding of the regulatory
effects of blood flow, adhesion receptor expression, and chemokines on inflammatory
responses and blood clotting.
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