The goal of this proposal is to obtain a new state-of-the-art atomic force microscope (AFM) to replace the fourteen-year-old outdated system in the Microscopy Imaging Center (MIC) at the University of Vermont. This instrument would meet the increasing demand for advanced features not supported by the existing microscope and would sustain the need for efficient AFM imaging for years to come with a reliable, high performance system. Importantly, this AFM system will permit live and fixed cell and tissue imaging with its enhanced Z- range and resolution. The requested instrument will be essential for future cutting edge biomedical research for the UVM College of Medicine community, and a vital adjunct to the MIC. The rationale for a new system is to enhance and sustain our current AFM imaging capabilities with a broader range of sophisticated imaging applications. A modern AFM system will meet the increasing demand for specialized imaging, especially for investigations using live cells and thick tissues. The current fourteen-year-old AFM in the MIC is severely limited with respect to the allowable specimen thickness, and by its restricted resolution capabilities. Four laboratories have been identified as major users for the purpose of this application since they represent the majority of the projected demand for the requested instrument given their existing and proposed application requirements. All major users are well-funded investigators with PHS grants, whose expanding research requires the enhanced technical features and capabilities of a new AFM. Their research projects address areas of high importance in contemporary biomedicine, including cardiovascular disease and carcinogenesis. The addition of a new state-of-the-art AFM to the MIC is expected to meet the present and future high resolution imaging requirements of researchers at the University of Vermont.