http://smartech.gatech.edu/handle/1853/6031 Original work by students in the Department of Biomedical Engineering Search the Channel search http://smartech.gatech.edu/simple-search http://smartech.gatech.edu/handle/1853/24297 Title: Engineering cell adhesive surfaces that support integrin #### binding using a recombinant fragment of fibronectin <br/> <br/>Authors: Cutler, Sarah Melissa http://smartech.gatech.edu/handle/1853/22691 Title: Robust Muscle Synergies For Postural Control <br/> <br/>Authors: Torres-Oviedo, Gelsy <br/> <br/>Abstract: The musculoskeletal structure of the human and animal body provides multiple solutions for performing any single motor behavior. The long-term goal of the work presented here is to determine the neuromechanical strategies used by the nervous system to appropriately coordinate muscles in order to achieve the performance of daily motor tasks. The overall hypothesis is that the nervous system simplifies muscle coordination by the flexible activation of muscle synergies, defined as a group of muscles activated as a unit, that perform task-level biomechanical functions. To test this hypothesis we investigated whether muscle synergies can be robustly used as building blocks for constructing the spatiotemporal muscle coordination patterns in human and feline postural control under a variety of biomechanical contexts. We demonstrated the generality and robustness of muscle synergies as a simplification strategy for both human and animal postural control. A few robust muscle synergies were able to reproduce the spatial and temporal variability in human and cat postural responses, regardless of stance configuration and perturbation type. In addition inter-trial variability in human postural responses was also accounted for by these muscle synergies. Finally, the activation of each muscle synergy in cat produced a specific stabilizing force vector, suggesting that muscle synergies control task-level variables. The identified muscle synergies may represent general modules of motor output underlying muscle coordination in posture that can be activated in different sensory contexts to achieve different postural goals. Therefore muscle synergies represents a simplifying mechanism for muscle coordination in natural behaviors not only because it is a strategy for reducing the number of variables to be controlled, but because it represents a mechanism for simply controlling multi-segmental task-level variables. http://smartech.gatech.edu/handle/1853/22663 Title: Suppression of Osteoblast Activity by Disuse is Prevented by Low Magnitude Mechanical Loading through a Bone Morphogenic Protein-Dependent Mechanism <br/> <br/>Authors: Patel, Mamta Jashvantlal <br/> <br/>Abstract: Musculoskeletal pathologies associated with decreased bone mass, including osteoporosis and disuse-induced bone loss, affect millions of Americans annually. Many pharmaceutical treatments have slowed osteoporosis, but there is still no countermeasure for bone loss observed in astronauts. Additionally, high magnitude and low frequency impact has been recognized to increase bone and muscle mass under normal but not microgravity conditions. However, a low magnitude and high frequency (LMHF) mechanical load experienced in activities such as postural control has also been shown to be anabolic to bone. While several clinical trials have demonstrated that the LMHF mechanical loading normalizes bone loss in vivo, the target tissues and cells of the mechanical load and underlying mechanisms mediating the responses are unknown. As such, the objectives of this project are to analyze cellular and molecular changes induced in osteoblasts by LMHF loading and to investigate the utility of a LMHF mechanical load in mitigating microgravity-induced bone loss. The central hypothesis of the project is that simulated microgravity or disuse conditions induce bone loss by inhibiting expression of genes critical in regulating bone formation, osteoblast differentiation, and subsequent mineralization while a LMHF mechanical load prevents these effects. To test this hypothesis, we developed an in vitro disuse system using the Random Positioning Machine (RPM). For the first time, we reported systemic gene expression studies in 2T3 preosteoblasts using the RPM disuse system showing that 140 genes were altered by RPM exposure with over two-fold statistically significant changes. Moreover, we also utilized an independent simulator called the Rotating Wall Vessel (RWV) to partially validate the in vitro disuse systems and to confine the list of genes to those most critical in regulating bone formation. After comparative studies, we constricted the list to 15 commonly changed genes, three of which were not only decreased with disuse but also increased with mechanical loading in vivo. Furthermore, we employed the RPM disuse system to evaluate the mechanism by which a LMHF load mitigates bone loss. Exposure of osteoblasts to the RPM decreased both ALP activity and mineralization even in the presence of bone morphogenic protein 4 (BMP4), and the LMHF mechanical loading prevented the RPM-induced decrease in both markers. Mineralization induced by LMHF mechanical loading was enhanced by treatment with BMP4 and blocked by the BMP antagonist noggin, suggesting a role for BMPs in this response. In addition, LMHF mechanical loading rescued the RPM-induced decrease in gene expression of ALP, runx2, osteomodulin, parathyroid hormone receptor 1, and osteoglycin. These findings show that osteoblasts directly respond to LMHF mechanical loading, potentially leading to normalization or prevention of bone loss caused by disuse or microgravity conditions. The mechanosensitive genes identified here provide potential targets for pharmaceutical treatments that may be used in combination with LMHF mechanical loading to better treat osteoporosis, disuse-induced bone loss, or microgravity-induced bone loss. http://smartech.gatech.edu/handle/1853/22648 Title: Knowledge Discovery of Cell-cell and Cell-surface Interactions <br/> <br/>Authors: Su, Jing <br/> <br/>Abstract: High-throughput cell culture is an emerging technology that shows promise as a tool for research in tissue engineering, drug discovery, and medical diagnostics. An important, but overlooked, challenge is the integration of experimental methods with information processing suitable for handling large databases of cell-cell and cell-substrate interactions. In this work the traditional global descriptions of cell behaviors and surface characteristics was shown insufficient for investigating short-distance cell-to-cell and cell-to-surface interactions. This problem was addressed by introducing individual-cell based local metrics that emphasize cell local environment. An individual-cell based local data analysis method was established. Contact inhibition of cell proliferation was used as a benchmark for the effectiveness of the local metrics and the method. Where global, summary metrics were unsuccessful, the local metrics successfully and quantitatively distinguished the contact inhibition effects of MC3T3-E1 cells on PLGA, PCL, and TCPS surfaces. In order to test the new metrics and analysis method, a model of cell contact inhibition was proposed. Monte Carlo simulation was performed for validating the individual-cell based local data analysis method as well as the cell model itself. The simulation results well matched with the experimental observations. The parameters used in the cell model provided new descriptions of both cell behaviors and surface characteristics. Based on the viewpoint of individual cells, the local metrics and local data analysis method were extended to the investigation of cell-surface interactions, and a new high-throughput screening and knowledge discovery method on combinatorial libraries, local cell-feature analysis, was developed. PLGA/PCL combinatorial libraries were used as a prototype and a shaper and holder phenomenon involving MC3T3-E1 cells interacting with PCL islands was discovered. In summary, the viewpoint of individual cells casts new light on the study of cell-cell and cell-surface interactions and represents a novel methodology for developing new data analysis and knowledge discovery methods. The results of contact inhibition study and the shaper and holder model provide new knowledge, while the local data analysis method as well as the cell model of contact inhibition suggested novel approaches to study cell-cell and cell-surface interactions.