"Analyzing structures of biomolecules at the single molecule level by direct imaging on surface"
Dr. Kelvin Anggara
Max Planck Institute for Solid State Research, Stuttgart (Germany)

Diverse structures of biomolecules in living systems pose challenges for present analytical methods in analyzing their individual molecular structures. Ensemble-averaged measurement on molecules with extensive structural variation leads to loss of structural information for individual molecules. We herein bypass this problem by imaging and analyzing single biomolecules deposited intact on surfaces. Biomolecules were transferred to the gas-phase by electrospray, mass-selected, and soft-landed at a cold single-crystal metal surface, using the Electrospray Ion Beam Deposition (ESIBD) technique. The deposited molecules were subsequently imaged one-at-a-time by Scanning Tunneling Microscopy (STM) and interpreted by DFT calculations to reveal their individual structures on surface. We successfully applied our approach to glycans as well as lipids and proteins densely decorated with glycans, whose analyses remain intractable by current analytical methods. Critical to our success is the choice of surfaces to deactivate diffusion and dissociation of biomolecules on surface, as well as the systematic molecular manipulation by the STM tip to unfold the intact biomolecule on surface. The ESIBD+STM+DFT approach opens a new avenue to access individual structures of any biomolecules that can be electrosprayed and deposited onto a surface.