ABSTRACT Dynamics of Cellular Rigidity Sensing on the Micron and Sub-micron Scale

This thesis describes a study of the effect of environmental cues including physical attribute of the cellular environment on cellular force and force transduction. Different mechanical parameters such as geometry and rigidity of the substrate are controlled independently and forces exerted by cells were measured. The experimental system for this study is based on fabrication of micron and submicron pillar substrates and their surface functionalization and finally measurement of forces that cells exert to these substrates. In chapter 2, the interplay between the rigidity of the substrate and the cell’s force re-sponse was studied. Arrays of flexible PDMS pillars used to measure the pattern of traction force generation on matrices. Using three different pillar diameters (2, 1 and 0.5 microm-eters), and three different pillar stiffnesses for each diameter, we showed that cells treat larger, fibronectin-coated pillars fundamentally differently than sub-micron pillars during initial contact formation. In the case of larger pillars, mouse embryo fibroblasts generated a constant force per unit area of about 1 nN/µm2 on pillars of different stiffness by causing different displacements; whereas, the sub-micrometer pillars were displaced by about 60 nm irrespective of stiffness. In addition, micron-scale pillars are all pulled toward the center o