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Role of fibronectin in tumor development and joint lubrication

Posted on:2016-10-11Degree:Ph.DType:Thesis
University:Cornell UniversityCandidate:Andresen Eguiluz, Roberto CarlosFull Text:PDF
GTID:2474390017969296Subject:Engineering
Abstract/Summary:
Surfaces in biology are present everywhere, and how biomacromolecules and cells interact with them to form interfaces is crucial in cell biology, biotechnology and medicine. For example, biosensors are based on the specific recognition of sugars such as glucose in the glucose-sensors used by diabetic patients. Another example is found in cancer, where breast cancer cells secrete factors that interact with peripheral stromal cells (the interface) and alter their behavior. Another interesting example can be found in diarthrodial joints, such as the knee or the hip joint, where two opposing surfaces need efficient and durable interfacing as they slide against each other over the lifespan of a healthy person.;In the first part of this thesis, I present a direct quantitative correlation between the mechanics of the fibronectin extracellular matrix at the cellular scale and the conformation of fibronectin constituting the matrix at the molecular scale. Additionally, I analyze the effects of mechanics and conformation on cell behavior (adhesion and secretion) in a model system that represents the interface with the tumor.;Next, I present a phenomenological study of the molecular interactions between fibronectin (present in the superficial zone of cartilage) and synovial fluid components. I do this by examining their synergistic performance under confinement and shear to provide efficient lubrication. These results are compared with the tribological performance of a mimetic lubricin developed by my coworkers.;Combined, these results have important implications for our understanding of (i) tumor development and vascularization (ii) cell-matrix interactions (by providing new insights into the structure-mechanics relationship of protein networks), and (iii) the molecular mechanisms of boundary lubrication and wear protection of articular surfaces. The findings presented in this work may be applied to future treatments of diseases such as breast cancer and osteoarthritis.
Keywords/Search Tags:Present, Fibronectin, Tumor
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