Bart Hoogenboom

High-resolution atomic force microscopy in liquid Solid-liquid interfaces Single-molecule biophysics Molecular machines Membrane proteins Contact details: Office: Room B101 Tel: +44(0)20 7679 0606 Extension: 30606 Fax: +44 (0)20 7679 0595 Email: b.hoogenboomucl.ac.uk

Research Interest
I am fascinated by the opportunities of nanotechnological tools to study and manipulate single atoms and molecules. I believe that there is a particular interest in exploiting these tools to investigate the molecular machines that make the biological cell function in a way similar to a macroscopic factory and yet - because of their nanometre-scale size and the presence of an aqueous environment - so different.

My research has a strong focus on scanning probe techniques. Of all scanning probe microscopes, the atomic force microscope (AFM) is the most popular for biological applications. Using an extremely sharp tip, it allows to scan a surface just like a person's fingertip reading Braille, “touching” and “feeling” single molecules and/ or atoms. Moreover, since the AFM can be operated in liquid, we can probe and image biomolecules under conditions that are very near to those in a living cell.

Precise control of the AFM cantilever, our miniature "fingertip", is crucial to gently probe molecules without damaging or distorting them. In our laboratory, we develop new techniques to get complete control of the cantilever in aqueous environment, with the aim of probing and imaging biologically relevant samples with sub-molecular or even atomic resolution. We apply these techniques to a variety of samples, preferably to molecules of biomedical relevance.

Biography

• 2007-present, Lecturer in the London Centre for Nanotechnology and the Department of Physics and Astronomy, University College London
• 2005-2007, Post-Doctoral Research Assistant, Biozentrum, University of Basel, Switzerland, Laboratory of Prof. Andreas Engel
• 2002-2005, Post-Doctoral Research Assistant, Department of Physics, University of Basel, Switzerland, Laboratory of Prof. Hans Hug
• 1998-2002, Ph. D. Condensed Matter Physics, University of Geneva, Switzerland, Laboratory of Prof. Øystein Fischer
• 1998, M. Sc. Surface Physics, University of Groningen, the Netherlands, Laboratory of Prof. George Sawatzky

Selected Publications

• B. W. Hoogenboom, K. Suda, A. Engel, and D. Fotiadis, “Supramolecular assemblies of the voltage-dependent anion channel in the native membrane”, J. Mol. Biol. 370, 246 (2007) [online article] [front cover]

Voltage-dependent anion channels (VDACs) play an important role in interfacing between the mitochondrial and cellular metabolisms and are believed to be a key protein in mitochondria-mediated apoptosis (programmed cell death). High-resolution, frequency-modulation AFM topographs show how VDAC is organised (from mono- to oligomers) in the native mitochondrial outer membrane.

• B. W. Hoogenboom, H. J. Hug, Y. Pellmont, S. Martin, P. L. T. M. Frederix, D. Fotiadis, and A. Engel, “Quantitative dynamic-mode scanning force microscopy in liquid”, Appl. Phys. Lett. 88, 193109 (2006). [online article] [News Feature in Nature on this research]

The resolution of AFM images on biological molecules strongly depend on the forces between the cantilever tip and the sample. Using a frequency-modulation technique in aqueous environment, these forces can be precisely measured, controlled and minimised, thus preventing the tip from damaging or dislodging the molecules that are investigated. The advantages of this technique are illustrated by true atomic-resolution images of mica and molecular-resolution images of the membrane protein bacteriorhodopsin, all in physiological buffer solution.

• B. W. Hoogenboom, P. L. T. M. Frederix, J. L. Yang, S. Martin, Y. Pellmont, M. Steinacher, S. Zaech, E. Langenbach, H.-J. Heimbeck, A. Engel, and H. J. Hug, “A Fabry-Perot interferometer for micrometer-sized cantilevers”, Appl. Phys. Lett. 86, 074101 (2005). [online article]
  

There is a general tendency to further miniaturise cantilevers for atomic force microscopy and cantilever sensing applications, thus reducing the effect of thermal noise on the measurement. Using a Fabry-Perot interferometer, sub-picometre oscillations of small cantilevers can be detected in vacuum, air and liquid. The interferometer can easily be aligned using a three-axis piezo-electric motor, and is particularly suited for atomic force microscopy.

• B. W. Hoogenboom, K. Kadowaki, B. Revaz, M. Li, Ch. Renner, and Ø. Fischer, “Linear and field-independent relation between vortex core state energy and gap in Bi₂Sr₂CaCu₂O_8+d”, Phys. Rev. Lett. 87, 267001 (2001) [online article]
  

Vortex cores in high-temperature superconductors can be regarded as a frozen-in version of the non-superconducting state above the critical temperature. This makes them of key importance to better understand the electronic properties of these materials. Using scanning tunnelling microscopy and spectroscopy, the electronic properties of the vortex cores of Bi₂Sr₂CaCu₂O_8+d are shown to strongly deviate from those in conventional superconductors. Moreover, the relevant energy scale is found to be proportional to the superconducting gap.

Research

Figure 1: Atomic and molecular resolution in liquid. The forces between cantilever tip and sample can be precisely determined from shifts in the cantilever resonance frequency (frequency-modulation AFM). Combined with a highly-sensitive deflection detector, this technique allows atomic-resolution images (left, showing atomic-scale defects) of mica and molecular-resolution images of the membrane protein bacteriorhodopsin (right, here imaged in a 2D lattice), all in physiological buffer solution.

Figure 2: VDAC in the native membrane. Outer mitochondrial membranes were purified and adsorbed on a mica substrate. Subsequent frequency-modulation AFM images show the VDAC assembling in monomers, dimers, trimers, tetramers, hexamers and higher oligomers. VDAC, appearing as a ring in the image, has an outer diameter of about 5 nm.