The fundamental study of Lewis acid/base interactions presented in this dissertation demonstrates the role of these interactions in adhesive phenomena. The model systems investigated were representative of real substrates and soft, viscoelastic adhesives where, in one case, favorable acid/base interactions were possible which were not possible in the other. Inverse gas chromatography (IGC) and Infrared spectroscopy (IR) techniques were used to analyze the model adhesive in terms of its acid/base nature. The results of both experiments indicated, through negative enthalpies of acid/base interaction with acidic solvents, that the model adhesive poly(2-ethyl hexyl methacrylate) (PEHMA) exhibits the properties of a Lewis base. The near quantitative agreement of the results from both experiments validate these methods of determining acid/base interactions in polymeric systems. Fitting the enthalpies for acid/base interaction to Drago’s and Gutmann’s models brought out the importance of the electrostatic component of the interactions investigated. Furthermore, they illustrated the need to expand the existing datasets beyond organo-meta1lic compounds, and include more common organic solvents. Results from X-ray photoelectron spectroscopy (XPS) and scanning transmission electron microscopy (STEM) analysis of the model substrate, grade 2 titanium, pretreated via chromic acid (CAA) or sodium hydroxide anodization (PSHA), confirmed that oxides of very similar topology can be produced. Indicator dye studies revealed the CAA-Ti had a surface pH of below 3.0 and the PSHA-Ti had a surface pH of above 8.0. Bonds constructed from these analyzed materials were tested in peel and both systems exhibited good adhesion. However, the bonds in which favorable interactions were possible demonstrated superior interfacial performance. This improvement was seen in the bond’s ability to resist adhesive (interfacial) failure at debond rates at which other bonds failed. When the test geometry was changed such that the stress intensity at the interface was increased, the bonds in which acid/base interactions were favorable supported a higher peel load. / Ph. D.

Indiana University-Purdue University Indianapolis (IUPUI) / Mechanical force environment is a major factor that influences cellular homeostasis and remodeling. The prevailing wisdom in this field demonstrated that a threshold of mechanical forces or deformation was required to affect cell signaling. However, by using a fluorescence resonance energy transfer (FRET)-based approach, we found that C28/I2 chondrocytes exhibited an increase in RhoA activities in response to high shear stress (10 or 20 dyn/cm2), while they showed a decrease in their RhoA activities to intermediate shear stress at 5 dyn/cm2. No changes were observed under low shear stress (2 dyn/ cm2). The observed two-level switch of RhoA activities was closely linked to the shear stress-induced alterations in actin cytoskeleton and traction forces. In the presence of constitutively active RhoA (RhoA-V14), intermediate shear stress suppressed RhoA activities, while high shear stress failed to activate them. Collectively, these results herein suggest that intensities of shear stress are critical in differential activation and inhibition of RhoA activities in chondrocytes.

Indiana University-Purdue University Indianapolis (IUPUI) / It is increasingly recognized that mechanical properties of substrates play a pivotal role in the regulation of cellular fate and function. However, the underlying mechanisms of cellular mechanosensing still remain a topic of open debate. Traditionally, advancements in this field have been made using polymeric substrates of adjustable stiffness with immobilized linkers. While such substrates are well suited to examine cell adhesion and migration in an extracellular matrix environment, they are limited in their ability to replicate the rich dynamics found at cell-cell interfaces. To address this challenge, we recently introduced a linker-functionalized polymer-tethered multi-bilayer stack, in which substrate stiffness can be altered by the degree of bilayer stacking, thus allowing the analysis of cellular mechanosensitivity. Here, we apply this novel biomembrane-mimicking cell substrate design to explore the mechanosensitivity of C2C12 myoblasts in the presence of cell-cell-mimicking N-cadherin linkers. Experiments are presented, which demonstrate a relationship between the degree of bilayer stacking and mechanoresponse of plated cells, such as morphology, cytoskeletal organization, cellular traction forces, and migration speed. Furthermore, we illustrate the dynamic assembly of bilayer-bound N-cadherin linkers underneath cellular adherens junctions. In addition, properties of individual and clustered N-cadherins are examined in the polymer-tethered bilayer system in the absence of plated cells. Alternatively, substrate stiffness can be adjusted by the concentration of lipopolymers in a single polymer-tethered lipid bilayer. On the basis of this alternative cell substrate concept, we also discuss recent results on a linker-functionalized single polymer-tethered bilayer substrate with a lateral gradient in lipopolymer concentration (substrate viscoelasticity). Specifically, we show that the lipopolymer gradient has a notable impact on spreading, cytoskeletal organization, and motility of 3T3 fibroblasts. Two cases are discussed: 1. polymer-tethered bilayers with a sharp boundary between low and high lipopolymer concentration regions and 2. polymer-tethered bilayers with a gradual gradient in lipopolymer concentration.