BLOOD CELL MECHANICS, SURFACE AFFINITY AND ADHESION

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Deformability properties of blood cells are essential determinants of flow distribution in the microcirculation and also modulate cell aggregation, agglutionation, and phagocytic interactions. The objectives of this research are to quantitate the time-dependent mechanical properties of white blood cells, the energetics of blood cell deformation and chemical attraction in cell-cell adhesion, and the mechanics of separation of adhesive contacts. The free energy potential for cell aggregation quantitates the initial stage of cell-surface "recognition" which is an important factor in the removal of aberrant cells and material from the circulation, infection of cells by pathogens, arrest and margination of circulating white and tumour cells. The strength of adhesion (represented by the forces required to separate contacts) determines the viability of cell aggregates when exposed to disruption by shear forces in the circulation. The specific aims are designed to address the following general questions: what is the commonality and diversity of passive rheological properties amongst white blood cells? Are there distinguishing features between blood phagocytes? What are the intrinsic properties that represent active mechanical stresses generated by phagocytes and how can these properties be related to chemical reactions inside cells? What is the affinity that acts at long range to promote adhesion via specific agglutination reactions? What is the "fracture" energy per crossbridge that stabilizes adhesive contacts in oppostion to environmental forces? How do impingement forces play a role in agglutination reactions? Unique micromanipulation techniques are used to perform micromechanical tests of single cell deformability and cell-cell adhesion. The observations are recorded with a video microscope system. Surface binding and distribution of ligand-receptor complexes are measured with a video intensified, laser fluorometry system, coupled to the microscope system.