John F. Marko Northwestern University Department of Biochemistry, Molecular Biology, Cell Biology and Physics and Astronomy ABSTRACT I will discuss experiments examining chromatin structure, using novel micromechanical approaches. Experiments where chromatin is assembled onto single DNAs under precise force control permit study of details of nucleosome assembly and disassembly. My group has used this approach to measure absolute free energy and kinetic rates for cell-extract-based chromatin assembly reactions. I will also discuss a separate line of experiments where individual mitotic amphibian chromosomes are studied micromechanically, providing new information about chromatin packing and connectivity. Our experiments indicate that the non-DNA "protein scaffold" takes the form of disconnected "chromatin crosslinks", and also suggest a role for DNA entanglements in mitotic chromosome structure.