or observed for molecular machines, offer a unique way to study fundamental
theories of statistical mechanics associated with fluctuation-dissipation theorems.
Here, we describe the mechanics of two modular polymers, i.e., fibronectin and
oligomeric calix[4]arene catenanes under external force. Whereas fibronectin is a
native protein that displays irreversible rupture of protein domains upon extension,
the linked calix[4]arene catenanes allow re-formation of separated bonds on experimental time scales due to mechanical locks. In this context, two fundamental
questions were addressed. First, to what extent can proteins be stabilized by
exposure to compatible solutes and, second, can we investigate H-bond breakage
both close to equilibrium and also far from equilibrium using a single molecule.
We found that, addressing the first question, it is possible to drive the system into
a more coiled conformation but not to enhance the stability of the domains.
Preferential exclusion of compatible solutes such as ectoine forces the protein
into a more globular conformation, which is displayed by a reduced persistence
length. Calixarene catenanes mechanically arrest the system in close vicinity
after rupture. The loops therefore permit the reversible rupture and rejoining of
individual nanocapsules formed by the calix[4]arene catenanes. Addressing the
second question, experiments carried out by force spectroscopy using an atomic
force microscope in conjunction with MD simulations and stochastic modeling
revealed the presence of an intermediate state between the closed and open state
of a single nanocapsule. In summary, entangled nanocapsules are ideal model
systems for investigating the strength of hydrogen bonds on a single molecule
level with adjustable reversibility. Reversibility can be tuned by changing the
loop length, as demonstrated by MD simulations. Longer loop lengths drive the
system out of equilibrium by widening the potential, making rejoining highly
improbable. The system offers the opportunity to study the energy landscape of a
single (chemical) reaction as a function of molecular design and external force,
making it an ideal test bed for modern theories of nonequilibrium statistical
mechanics.
4 Mechanical Properties of Nucleic Acids with Binding
Pockets for Small Molecules
Mechanical properties of biopolymers such as nucleic acids, in particular of DNA,
have become of high interest in material science. As a programmable scaffold,
biopolymers can be designed to self-assemble into a variety of two- and threedimensional structures and thus form an interesting platform for bottom-up assembly
of nanoscale structures [151]. In addition to structures that can be predicted
and rationally designed by engineering standard interactions of the Watson–Crick
type, nucleic acids can establish noncanonical interactions to form complicated threedimensional structures, including catalytic pockets and high affinity binding pockets
for small molecules. Although such binding pockets cannot yet be rationally
52
R. Berger et al.
theories of statistical mechanics associated with fluctuation-dissipation theorems.
Here, we describe the mechanics of two modular polymers, i.e., fibronectin and
oligomeric calix[4]arene catenanes under external force. Whereas fibronectin is a
native protein that displays irreversible rupture of protein domains upon extension,
the linked calix[4]arene catenanes allow re-formation of separated bonds on experimental time scales due to mechanical locks. In this context, two fundamental
questions were addressed. First, to what extent can proteins be stabilized by
exposure to compatible solutes and, second, can we investigate H-bond breakage
both close to equilibrium and also far from equilibrium using a single molecule.
We found that, addressing the first question, it is possible to drive the system into
a more coiled conformation but not to enhance the stability of the domains.
Preferential exclusion of compatible solutes such as ectoine forces the protein
into a more globular conformation, which is displayed by a reduced persistence
length. Calixarene catenanes mechanically arrest the system in close vicinity
after rupture. The loops therefore permit the reversible rupture and rejoining of
individual nanocapsules formed by the calix[4]arene catenanes. Addressing the
second question, experiments carried out by force spectroscopy using an atomic
force microscope in conjunction with MD simulations and stochastic modeling
revealed the presence of an intermediate state between the closed and open state
of a single nanocapsule. In summary, entangled nanocapsules are ideal model
systems for investigating the strength of hydrogen bonds on a single molecule
level with adjustable reversibility. Reversibility can be tuned by changing the
loop length, as demonstrated by MD simulations. Longer loop lengths drive the
system out of equilibrium by widening the potential, making rejoining highly
improbable. The system offers the opportunity to study the energy landscape of a
single (chemical) reaction as a function of molecular design and external force,
making it an ideal test bed for modern theories of nonequilibrium statistical
mechanics.
4 Mechanical Properties of Nucleic Acids with Binding
Pockets for Small Molecules
Mechanical properties of biopolymers such as nucleic acids, in particular of DNA,
have become of high interest in material science. As a programmable scaffold,
biopolymers can be designed to self-assemble into a variety of two- and threedimensional structures and thus form an interesting platform for bottom-up assembly
of nanoscale structures [151]. In addition to structures that can be predicted
and rationally designed by engineering standard interactions of the Watson–Crick
type, nucleic acids can establish noncanonical interactions to form complicated threedimensional structures, including catalytic pockets and high affinity binding pockets
for small molecules. Although such binding pockets cannot yet be rationally
52
R. Berger et al.