|
Thursday,
September
14, 2000
8:00 Registration, Exhibit/Poster Set-up, Coffee and Danish
Force Generation by Molecular Motors
9:00 Chairperson’s Welcome and Opening Remarks
Viola Vogel, Ph.D., Director, Center for Nanotechnology, Department
of Bioengineering; Associate Professor, University of Washington
9:15 The Mechanism of Force Generation by Molecular Motors: Myosin
and Kinesin
Roger Cooke, Ph.D., Professor, Department of Biochemistry/ Biophysics,
University of California San Francisco
The mechanisms of myosin and kinesin are beginning to be understood
at the molecular level. In both motors nucleotides bind to the motor
domain, and induce conformational changes, which are amplified by a
second region, known as the neck. In the myosin motor the neck acts
as a simple lever arm to produce a 5-10 nm power stroke. In the kinesin
motor the neck undergoes a transition from an unstructured random coil
to a highly structured ß-sheet. This transition biases the binding
of the second head of kinesin towards the plus end of the microtubule,
thus producing an 8 nm power stroke.
9:45 Single Molecule Analysis of Biological Molecular Motors
Toshio Yanagida, Ph.D., Professor, Department of Physiology and Biosignaling,
Osaka University Graduate School of Medicine, Japan
We have developed several new technologies for single molecule imaging
and single molecule nano-manipulation of biomolecules in aqueous solution.
Using these technologies, we have studied how biological molecular motors
can work under the strong thermal agitation with high efficiency of
energy conversion.
10:15 Single Molecule Enzymology of Myosin Triphosphatase
David R. Trentham, Ph.D., Head, Division of Physical Biochemistry,
National Institute for Medical Research, United Kingdom
The mechanical properties of proteins explored at the single-molecule
level is central to a major evolving field in biology. In motor proteins
such properties are driven by chemical energy and frequently coupled
to ATP hydrolysis. This report focuses on the enzymatic activity of
the motor-protein myosin studied at the single -molecule level using
fluorescent analogs of ATP by means of total internal reflection fluorescence
(TIRF) microscopy.
10:45 Exhibit/Poster Viewing and Refreshment Break
11:15 How ATP Synthase Converts Chemical Energy into Mechanical Work
George Oster, Ph.D., Professor, Departments of Molecular and Cellular
Biology & ESPM, University of California, Berkeley
ATP synthase is the universal enzyme that synthesizes ATP, the universal
fuel that powers most cellular processes. This protein is constructed
from two rotary motors acting in opposition, and operating by two different
physical mechanisms. The F1 motor generates a mechanical torque using
the hydrolysis energy of ATP. The Fo motor generates a rotary torque
in the opposite direction employing a transmembrane proton motive force.
The two motors are connected by a flexible coupling, and each motor
can be reversed: the Fo motor can drive the F1 motor in reverse to synthesize
ATP, and the F1 motor can drive the Fo motor in reverse to pump protons.
Thus ATP synthase exhibits two of the major energy transduction pathways
employed by the cell to convert chemical energy into mechanical force.
A physical analysis of the F1 and Fo motors can provide a unified view
of the mechanochemical principles underlying these energy transducers.
11:45 Engineering Life into Nanofabricated Devices
Carlo Montemagno, Ph.D., Associate Professor, Department of Biological
Engineering, Cornell University
Presented will be the details for fabricating nanomechanical devices
powered by molecular motors including results of the first, functional
biomolecular motor powered nanomechanical device ever successfully fabricated.
Included will be experimental results of efforts to incorporate such
devices into living cells and in the creation of submicron sized “Smart
Dust” (i.e. autonomous sensor systems).
12:15 Speaker Roundtable
Luncheon
Delegates are invited to join participating speakers during lunch to
informally discuss their presentations and “hot topic” issues
related to molecular motors.
1:40 Chairperson’s Remarks
Peter Satir, Ph.D., University Chairman, Department of Anatomy and
Structural Biology, Albert Einstein College of Medicine
1:45 Surface-Mounted Dipolar Molecular Rotors
Josef Michl, Ph.D., Professor, Department of Chemistry and Biochemistry,
University of Colorado
Theoretical simulation and analysis and experimental approach to dipolar
rotors mounted on grids and surfaces and driven by a rotating electric
field or a stream of gas will be described.
2:15 Force Generation by Kinesin and Nanoactuatoric Developments
Eberhard Unger, Ph.D., Professor and Head of Molecular Cytology Department,
Institute of Molecular Biotechnology, Jena, Germany
Kinesin is a motor protein which translocates cell organelles along
specialized filamentous tracks, so-called microtubules. The translocation
is directed by microtubule polarity and intrinsic kinesin properties.
This process of biological force generation can also be realized outside
cells. The in vitro approaches of kinesin-mediated transport of large
loads require an isopolar arrangement of parallel aligned microtubules.
Controlling transport direction is an essential step for future developments
of motor protein-based nanoscaled devices. I will present the assembly
of highly ordered force-generating arrays, conditions of force regulation,
and give implications for the development of nanoactuatoric devices.
2:45 Solar Power for Molecular Motors
Devens Gust, Ph.D., Professor and Chair, Department of Chemistry
and Biochemistry, Arizona State University
Biological molecular-scale motors are typically powered directly by
transmembrane proton motive force, or by high-energy chemicals such
as ATP. For most living things, the ultimate energy source is sunlight.
Photosynthesis converts light energy to electrochemical potential energy
in the form of transmembrane charge separation. This is used to pump
hydrogen ions across the membrane, creating proton motive force (pmf).
Finally, ATP synthase uses the proton motive force to make ATP from
ADP and inorganic phosphate. It is now possible to prepare liposome-based
semi-synthetic constructs that are able to mimic these energy transduction
processes. Such constructs could be used to power a variety of natural
or biomimetic molecular motors.
3:15 Directing the Translational Motion of Motor Proteins in Synthetic
Environments: Learning How to Build Molecular Shuttles
Viola Vogel, Ph.D., Director, Center for Nanotechnology, Department
of Bioengineering; Associate Professor, University of Washington
Nature has evolved motor proteins to shuttle molecular cargo within
cells over long distances and against concentration gradients. It is
of fundamental technological interest to learn how to control the translational
motion of motor proteins in non-biological environments. One application
is to use motor proteins to transport molecular cargo between user-specified
locations which is a first step in building molecular assembly lines
and a major challenge in nanotechnology. We will discuss how to direct
the translational motion of microtubules over long distances in non-biological
environments via properly engineered nanoscale tracks, and how to regulate
their speed non-invasively.
3:45 Exhibit/Poster Viewing and Refreshment Break
4:15 Cilium as a Biological Nanomachine
Peter Satir, Ph.D., University Chairman, Department of Anatomy and
Structural Biology, Albert Einstein College of Medicine
The cilium is used by many cells, including a number of human cells
for swimming or to propel viscous media. Some 250 different proteins
assemble into the 9+2 axoneme, the ca. 200 nanometer diameter functional
cytoskeleton, the axonema of the cilium. The axoneme changes shape by
bending caused by the microtubule-sliding driven by a series of isoforms
of the molecular motor, dynein. The frequency of ciliary beat and the
bend form are controlled by changes in the velocity and extent of the
microtubule sliding. These parameters can be manipulated in aqueous
solution by simple changes in solution composition to produce useful
work.
4:45 Regulation of Kinesin Motor Activity At the Level of the Microtubule
Track
Gregg Gundersen, Ph.D., Associate Professor, Department of Anatomy
& Cell Biology, Columbia University
For kinesin motors to perform useful work in cells, their activity must
be regulated both temporally and spatially. We have been studying the
role that ost-translational modifications of tubulin may have in regulating
the activity of kinesin. Our in vitro studies suggest that tubulin post-translational
modification can regulate the binding and ATPase activity of kinesin.
In cells, we have observed results for a number of organelle systems
suggesting that cells use post-translationally modified microtubules
to spatially regulate the activity of kinesin motors. The response of
kinesin motors to different post-translationally modified microtubules,
suggests it may be possible to design specificity and selectivity into
substrata for nanomotors.
5:15 Structural Changes that Drive Myosin Molecules Along Actin Filaments
Peter J. Knight, Ph.D., Lecturer, School of Biomedical Sciences,
University of Leeds, United Kingdom
Myosin motor molecules move along actin by making structural changes
after attaching. The myosin family of proteins is diverse, reflecting
adaptations for fulfilling distinct functions in the living cell. We
will discuss recent progress in understanding the structural mechanism
of movement of these proteins at the single molecule level.
5:45 Close of Day One
Friday,
September 15, 2000
8:30 Exhibit/Poster Viewing, Coffee and Danish
9:00 Chairperson’s Remarks
Eberhard Unger, Ph.D., Professor and Head of Molecular Cytology Department,
Institute of Molecular Biotechnology, Jena, Germany
9:15 Selected Oral Poster Presentations
Bio/Synthetic Use of Molecular Motors for Nanotech Applications
9:45 Light-Driven Synthetic Molecular Motors
Ben L. Feringa, Ph.D., Professor of Organic Chemistry, Department
of Organic and Molecular Inorganic Chemistry, University of Groningen,
The Netherlands
The design, synthesis and properties of photoactive materials, that
can function as molecular motors and form the key elements for the construction
of molecular type machinery, are discussed. Chirality is one of the
most intriguing features of living organisms and the precise control
of chirality at the molecular and supramolecular level is essential
for structure and function in biosystems. In the approaches toward molecular
motors that will be reported the photochemical modulation of chirality
is accomplished and it is shown that the energy from the light is used
to accomplish unidirectional molecular type rotary motion. Molecular
control of switching, organization and motion are all essential to the
ultimate construction of advanced motors and several experimental approaches
will be reported.
10:15 Conducting Polymer Molecular Muscles
John D. Madden, Ph.D., BioInstrumentation Laboratory, Massachusetts
Institute of Technology
Conducting Polymer materials offer properties enabling the creation
of biomimetic artificial muscles. Polypyrrole-based actuators, for example,
generate forces per cross-sectional area that are up to two orders of
magnitude greater than human muscle with equal power to mass ratios.
In these traditional Conducting Polymer devices, work is generated by
the movement of ions into or out of the bulk polymer matrix. We are
currently investigating a new class of Conducting Polymers in which
actuation results from conformational changes along the molecular backbone.
10:45 Exhibit/Poster Viewing and Refreshment Break
11:15 Towards a Chemically Driven Molecular Electron Pump
Imre Derenyi, Ph.D., Fellow, Collegium Budapest, Hungary; Fellow,
Physical Chemistry Institut Curie, France
Charge can be pumped through a tiny gated portal by cyclically modulating
the portal and gate energies. We show that randomly switching between
two configurations of portal and gate energies, with exponentially distributed
lifetimes in each configuration, can support efficient pumping and provide
a mechanism for chemically driven electron pumping through a molecular
wire. Aside from being of tremendous intellectual interest and possibly
shedding light on the function of biological electron transport proteins,
a chemically driven electron pump could play a role in the design of
molecular computers, acting as a molecular device that uses a chemical
reaction to power, gain and prevent dissipation of an input signal traveling
through the molecular computational circuit.
Biomedical Applications of Molecular Motors
11:45 Implantable Molecular
Factories
Mauro Ferrari, Ph.D., Professor of Internal Medicine, Professor of
Mechanical Engineering, Director, Biomedical Engineering Center, The
Ohio State University; Chairman, Ohio MicroMD: The BioMEMS Consortium
on Medical Therapeutics; Editor-in-Chief, Biomedical Microdevices: BioMEMS
and Biomedical Nanotechnology
Our laboratories are pursuing the vision of implantable cell bioreactors,
both of the cellular and molecular type, with the objective of providing
physiologically delivered medical therapy. The first indication we have
pursued is Type I insulin-dependent diabetes mellitus, for which we
employ a micromachined immunoisolation biocapsule with nanopore permselective
external surfaces. Molecular bioreactors will also be introduced in
this presentation.
12:15 Molecular Motors as Therapeutic Targets in Human Medicine
James Sabry, M.D., Ph.D., President and CEO, Cytokinetics, Inc.
The human genome contains a rich array of molecular motor proteins that
carry out a large number of highly specific tasks. Many of these tasks
are integrated into biological pathways that are known to be important
for disease treatment. We are developing technologies to interrogate
these proteins with small molecule compounds and to develop these compounds
into a novel class of therapeutics for cancer, cardiovascular disease,
infectious and inflammatory disease and neurological disorders.
12:45 Chairperson’s Remarks and Close of Conference
|
