Project Summary Temperature is critical to all life activities and regulates biological processes at various levels. Cells not only detect temperature changes through their unique temperature-sensitive molecular machineries but also adapt with appropriate responses to maintain their inherent functions. Despite the fundamental involvement of temperature in biological processes, the molecular mechanism by which cells produce and use heat is largely unknown. Our aim to develop atomically precise nanoarchitectures as both stimulators and thermometers to study various temperature-sensitive molecules down to the sub-cellular level. The study will investigate spatio-temporal temperature variations, including organelle-specific thermogenesis to develop the intrinsic connections between temperature and cell functions. The proposed study will combine nanoarchitectures with our recent demonstrated ultrafast optical spectroscopy, structural characterizations, and atomistic-to-microscope multiscale modeling framework to design, measure, and analyze the molecular-level thermal-biological interactions. The new approach will quantify intracellular temperature changes at the microscopic level in large difference from those assumed at a water environment at the macroscopic level. We expect the employment of new nano-architecture will uncover novel mechanisms and fundamental understandings of intracellular temperature-assisted functions.