The interplay of cell tension, elasticity, and adhesion: From the simple red cell membrane to differentiation and signaling muscle cells
Cellular processes ranging from survival to motility to differentiation are increasingly understood to depend on the collective interplay of tension, elasticity and adhesion. The focus of this thesis has been to add experimental and computational insights into the role of these factors in basic biological processes ranging from passive adhesion of a simple cell membrane to contractility-modulated cell attachment in sensing, signaling and differentiation. In simple membrane-based systems like red blood cells, we show that passive adhesion induces tension that not only alters how they are probed by the AFM but also influence molecular attachment dynamics. In the muscular dystrophies, perturbations in the dystroglycan complex leads to integrin upregulation as a natural compensatory process, with dramatic upregulation of paxillin generating a stiffer, hypercontractile or hypertensive state in these diseased cells. Stretch activation of FAK-paxillin-MAPK pathway observed in both normal and dystrophic muscle, is surprisingly absent under osmotically induced stress, highlighting signaling differences when stresses are imposed normal to the membrane or parallel to it. Cell sensing of extracellular matrix is studied with a finite element model in which an adherent cell placed on an elastic matrix is modeled as prestressed and firmly attached hyperelastic solids. One key question addressed is the enhanced spreading behavior observed on soft and thin matrices compared to stiff matrices, which ties into the stiffness-sensitive differentiation of muscle and stem cells. Average interfacial strains between cell and matrix show large deviations only when soft matrices are a fraction of the height and width of a cell, proving consistent with experiments. ^
Engineering, Biomedical|Engineering, Mechanical
"The interplay of cell tension, elasticity, and adhesion: From the simple red cell membrane to differentiation and signaling muscle cells"
(January 1, 2007).
Dissertations available from ProQuest.