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a.
Bio-Molecular
Motility – where Physics meets Biotech
Physicists
have a long history of making substantial contributions to our
understanding of life. One of the first prominent examples is Erwin
Schrödinger, who used general entropic arguments to show the necessity of
macromolecular coding of life.[i]
This seminal insight had a profound impact on the search for (and
subsequent discovery of) DNA. More recently, the availability of powerful
techniques, which physicists and engineers have developed for the “hard
sciences”, has led to a distinct change in the research patterns in the
life sciences: it enables controlled in-vitro experiments are now possible
in place of in-vivo experiments. This seemingly benign step should not be
underestimated. The descriptive nature of the early life sciences can be
attributed to the overwhelming complexity of the in-vivo systems being
studied, which often prevented sufficiently controlled experiments. With
more controlled experiments causality can often better be established,
which has introduced a more predictive approach to the life sciences. The
study of interactions between and self-assembly of bio-molecular systems
is one such area. Insights from surface science, coupled with experimental
designs arising from nanotechnology now enable rather sophisticated
in-vitro experiments. It is this general area that our studies on
bio-molecular motility exploit. Specifically, we artificially fabricate
the motor protein kinesin and the microtubular tracks on which these
kinesin motors travel as well as lithographic electrodes to
electrophoretially attract them to surfaces.[ii],[iii]
Because we can control the specific properties of the constituents and the
surface interactions on an artificial chip we can precisely analyze the
resulting kinetic processes and determine causalities in the behavior. As
a result, we could determine some of the underlying parameters and
fabricate transport systems for a wide range of physical materials,
ranging from quantum dots to carbon nanotubes.[iv],[v],[vi],[vii],[viii],[ix]
Bio-motility systems,
comprising of microtubules (MTs) and kinesin, can provide molecular
insight into neuronal transport and communication, with significant
potential to understand diseases of societal impact.
We have developed lab-on-a-chip based assays to mimic protein-protein
interactions and to model motor protein movement, relevant to cellular
mechanics. Changes of the biochemical nature of the microenvironment can
alter the interaction of the sensory motif of the protein in cellular
transport. Altering the environment with an inhibitor of protein dynamics
at the mesoscopic scale (as shown in our rendering on the right),[x],[xi],[xii] we have
investigated the co-relation of engineered proteins by using time lapse
fluorescence microscopy and the mathematical modeling of particle
dynamics.[xiii] In order to
better understand the biomedical relevance of these in-vitro results, the
relation to cellular systems needs to be investigated.
b.
Modifying the
Graphene Surface by Local Electron Irradiation
Graphene is one of the most interesting materials for
both fundamental and applied studies. Arising from the deceptively simple
hexagonal organization of carbon in a monatomic sheet, the unusual
electronic as well as mechanical properties are of interest. Our research
is focused at our ability to locally alter the properties of graphene by
inducing damage sites through electron beam patterning thus encoding
lateral functional structure directly in the graphene sheet. We can do
this by using the computer controlled electron beam in a nanopatterning
system to locally functionalize the electronic properties which then can
be measured through a 4-wire electronic measurement. As a result of the
electron irradiation we have measured changes of the electronic
properties, consistent with altered adsorption behavior on the graphene
surface.
[xiv],[xv]
c.
Low Temperature
Scanning Tunneling Microscopy of Single Molecule Magnets
Single molecule magnets (SMMs) are macromolecular
complexes composed of a magnetic core stabilized by organic ligands. The
magnetic core of a typical SMM contains a number of magnetic centers which
behave more or less independently at high temperature. As the temperature
is lowered, the magnetic system enters a correlated state, i.e. the
independence of the magnetic centers ceases as the entire molecule is
governed by a correlated magnetic system. The ground state of this system
is bi-stable with a substantial energy barrier preventing thermally
activated transitions. As a result, the molecules can be prepared in a low
temperature state which allows transitions only in a resonance tunneling
event, called macroscopic quantum tunneling. This phenomenon accounts for
a large part of the fundamental interest in this class of magnetic
systems. In addition, substantial applied potential arises from these
molecules facilitating quantum computing and data storage at the single
molecule level. The most suitable instrument to study the intramolecular
magnetic system at low temperature (T<3K) is a scanning tunneling
microscope that allows the in-situ application of a magnetic field in all
3 dimensions (vector magnet). This type of system permits the in-situ
alignment of the magnetic field direction with the relevant magnetic axis
of the molecule while performing electronic tunneling measurements with
sub-molecular resolution at low temperature. There are only a handful of
instruments in the world that allow the simultaneous application of these
conditions (particularly the vector magnet) and thus a suitable single
molecule experiment. We have access to one of these instruments at Tohoku
University’s AIMR and have performed some of the first experiments in this
direction.[xvi]
In collaboration with mathematicians, we have developed a general model to
predict molecular stability based on graph theory,[xvii],[xviii]
a concept which we are currently extending to include magnetic moments.
[i] Erwin
Schrödinger, “What is life?”, Cambridge University Press (1992).
[ii]
J. A. Noel, W. Teizer,
and W. Hwang, ACS
Nano 3, 1938 (2009).
[iii]
J. Noel, W. Teizer, and W.
Hwang, Journal of Visualized Experiments
30 (2009).
[iv] A. Sikora, J.
Ramon, K. Kim, K. Reaves, H. Nakazawa, M. Umetsu, I. Kumagai, T.
Adschiri, H. Shiku, T. Matsue, W. Hwang and W. Teizer. Nano
Letters 14, 876-881
(2014).
[v]
K. Kim, A. L. Liao, A. Sikora, D. Oliveira, H.
Nakazawa, M. Umetsu, I. Kumagai, T. Adschiri, W. Hwang and W.
Teizer. Biomedical Microdevices
16, 501-508 (2014).
[vi]
K. Kim, A. Sikora, K. S. Nakayama,
H. Nakazawa, M. Umetsu, W. Hwang and W. Teizer.
Applied Physics Letters
105, 143701-1–143701-5 (2014).
[vii]
K. Kim, A. Sikora, K. S. Nakayama,
M. Umetsu, W. Hwang and W. Teizer. Journal of Applied Physics
117, 144701-1–144701-10 (2015).
[viii]
A. Sikora, J. Ramón-Azcón, M. Sen, K. Kim, H. Nakazawa,
M. Umetsu, I. Kumagai, H. Shiku, T. Matsue and W. Teizer.
Biomedical Microdevices 17,
78:1-6 (2015).
[ix]
A. Sikora, F. F. Canova, K. Kim, H. Nakazawa, M.
Umetsu, I. Kumagai, T. Adschiri, W. Hwang, W. Teizer. ACS Nano
9, 11003-11013 (2015).
[x]
S. Bhattacharyya, K. Kim, and W. Teizer.
Advanced Biosystems
1, 1600034 (2017).
[xi]
S. Bhattacharyya, K. Kim, H. Nakazawa, M. Umetsu, and
W. Teizer. Integrative
Biology 8,
1296-1300 (2016).
[xii]
S. Bhattacharyya,
K. Kim, and W. Teizer. Advanced Biosystems
1, 1700108 (2017).
[xiii]
K. Kim, A. Sikora, K. S. Nakayama,
H. Nakazawa, M. Umetsu, W. Hwang and W. Teizer.
Physical Biology 13, 056002
(2016).
[xiv] S. O. Woo and
W. Teizer. Applied Physics Letters
103, 041603 (2013).
[xv]
S. O. Woo and W. Teizer. Carbon
93, 693-701 (2015).
[xvi]
K. Reaves, K. Kim, K.
Iwaya, T. Hitosugi, Helmut G. Katzgraber, H. Zhao, K. R. Dunbar,
W. Teizer, SPIN 03, 1350004 (2013).
[xvii]
D. M. Packwood,
K. T. Reaves,
F. L. Federici, H. G. Katzgraber and W. Teizer.
Proceedings of the Royal Society A
469,
20130373 (2013).
[xviii]
D. M. Packwood, H. G. Katzgraber, W. Teizer.
Proceedings of the Royal
Society A 472,
20150699:1-19 (2016).
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