DOI: 10.1002/adma.200801291
Biomolecular Motor-Powered Self
Nanocomposite Rings**
By Haiqing Liu, Erik D. Spoerke, Marlene Bachand, S
George D. Bachand*
Thermodynamic relaxation can generate complex nanos-
tructured materials via self-assembly; these structures, how-
ever, are ultimately limited by chemical equilibria and
diffusional transport processes.[1] In contrast, living systems
use a concerted combination of thermodynamic and energy-
dissipating processes to remove these functional limitations,
and generate complex, structured materials with a wide range
of adaptive and emergent behaviors. An underlying principle
of such systems involves the dynamic self-assembly of
materials, which occurs outside of thermodynamic equilibrium,
requires a source of energy, and bridges multiple length
[2–4]
(SQDs) and assembling the nanocomposite rings. Microtu-
ization of tubulin
iameter and 10–
icrotubules were
nd had an
ontribute
omposite
rigidity of
taxol-stabilized microtubules is
2.0 10 N m2.[15] The
energy-dissipating component involves the chemo-mechanical
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Materials Sciences and Engineering in the Department of Energy
447694AL85000. Supporting Information is available online from Wiley
InterScience or from the author.polymerized according to published protocols,[13,14] a
average length of
20mm. The microtubules c
considerable mechanical strain energy to the nanoc
rings based on its relatively rigid nature; the flexural
24
Office of Basic Energy Sciences and Sandia’s Laboratory Directed
Research and Development Office. Sandia is a multiprogram
laboratory operated by Sandia Corporation, a Lockheed Martin
Company, for the United States Department of Energy’s National
Nuclear Security Administration under Contract DE-AC04-bules are formed by the GTP-driven polymer
dimers into hollow cylinders of
25 nm in d
20mm in length. In this study, biotinylated m
Dr. Peng Li in the Transmission Electron Microscopy Laboratory at
the University of New Mexico for technical assistance on STEM work,
and Dr. J. Howard for generously providing the Drosophila kinesin
expression clone. This work was supported by the Division ofscales. Analogous principles have been applied to assemble
a broad range of artificial ‘‘dissipative’’ structures[5] through
electrorheological,[6] magnetohydrodynamic,[7] electrohydro-
dynamic,[8] and magnetorheological,[9] interactions that induce
spatiotemporal ordering. Efforts to understand these effects
have led to significant insights into fundamental nonequili-
brium physics.[10] While these approaches expand the practical
range of materials, they rely on programmed or user-defined
stimuli to drive the assemblies out of equilibrium. The next
major step in developing materials assemblies will involve self-
regulating systems that define the dynamic assembly and
adaptive behavior of materials. Such feedback-regulated
systems will extend the functional nature of nanostructured
[*] Dr. G. D. Bachand, Dr. H. Liu, M. Bachand, Dr. S. J. Koch
Biomolecular Interfaces and Systems Department,
Sandia National Laboratories
P.O. Box 5800, MS-1413,
Albuquerque, NM 87185 (USA)
E-mail: gdbacha@sandia.gov
Dr. E. D. Spoerke, Dr. B. C. Bunker
Electronic and Nanostructured Materials Department,
Sandia National Laboratories
P.O. Box 5800, MS-1411,
Albuquerque, NM 87185 (USA)
[**] We thank Drs. Andy Boal, Peter Feibelman, and Gordon Osbourn for
helpful discussion and comments on this manuscript. We thank
2008 WILEY-VCH Verlag Gmb-Assembly of Dissipative
teven J. Koch, Bruce C. Bunker, and
materials to include revolutionary behaviors (e.g., adaptive
reconfiguration and self-healing), currently unattainable by
conventional self-assembly methods.
There are few examples of dynamic self-assembly in which
the energy component is intrinsic to the system, as opposed to
externally applied (e.g., electromagnetic fields). One system
involves the dynamic assembly of nanospools[11,12] and
nanocomposite rings[13] wherein assembly is achieved through
a stochastic interaction of energy-dissipation and thermo-
dynamic processes. One remarkable characteristic of both
structures is the significant energy (i.e., >105 kT) that is
required for their formation, which is based on the relatively
high bending rigidity of the microtubules.[11] This energy input
is cooperatively supplied through the hydrolysis of ATP by
kinesin (energy dissipation) and the formation of multiple
biotin–streptavidin bonds (thermodynamic). In addition, the
nanospools display a highly nonequilibrium existence in which
the unzipping of biotin–streptavidin bonds by kinesin motor
leads to the spontaneous unspooling for the structures.[11] A
unique aspect of the nanocomposite rings concerns the ability
to assemble quantum dots across multiple length scales. The
microtubules in these structures serve as a nanoscale scaffold
for assembling the quantum dots; the quantum dot-laden
microtubules subsequently self-organize into microscale,
optically active structures.[13] While the properties of these
nonequilibrium structures have been described, the mechan-
ism of their formation is unknown and may provide valuable
insight with respect to developing dynamic assembly processes
for the synthesis of nanostructured materials. Thus, the
purpose of this study was to characterize the fundamental
mechanisms by which biomolecular motors drive the assembly
and disassembly of the composite ring structures.
The individual components and energetics involved in the
assembly of the nanocomposite rings are depicted in Figure 1.
In this system, biotinylated microtubule filaments serve as the
primary scaffold for binding streptavidin-coated quantum dotsH & Co. KGaA, Weinheim Adv. Mater. 2008, 20, 4476–4481

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microtubules and formation of an oligomer (i.e.,
two or more microtubules bound together to form
an extended structure). Oligomer formation
occurred almost immediately after introduction
of the SQDs. The thermodynamic energy asso-
ciated with biotin–streptavidin bonds served to
attach the microtubule units together into oligo-
mers (Fig. 3a and b), which were still capable of
being linearly translated by the motors. Scanning
transmission electron microscopy (STEM) of the
oligomers revealed the presence of mechanically
constrained domains (Fig. 3c and d), including
repeating domains (
200 nm in length) of coiled-
coil helical and kinked structures formed within the
oligomers. We attribute the formation of these
domains to axial rotation of the oligomers by the
kinesin motors. Axial rotation of microtubules
occurs during kinesin transport when the number of
protofilaments is greater or less than 13.[14] We
postulate that axial rotation of microtubules within
the population induced winding of the oligomers,
and the formation of the observed twisted and
kinked domains (Fig. 3c and d).
The next step in nucleation involved the bending of the
translate bio-
. The kinesin
to the linear
added to the
n of biotin–
stored in the
il and kinkedtransduction associated with kinesin biomolecular motors in
the form of ATP hydrolysis (12 kcal mol1) and the
generation of
40 pN nm (6 kcal mol1) of mechanical work,
with an overall efficiency of
50%.[16,17] A kinesin-1 from
Drosophila melanogaster was purified as previously
described[18] and used in gliding motility assay[19,20] to
assemble the nanocomposite rings. The forces produced by
the motors actively drive the translocation of microtubules
across a surface, and enable both assembly (bringing
components together and forcing them into place) and
Figure 1. The gliding motility geometry. Surface-adhered kinesin motors
tinylatedmicrotubule filaments, with attached nanoparticles, across a surface
motors dissipate chemical energy through ATP hydrolysis, which is coupled
translation and axial rotation of microtubules. Thermodynamic energy is
system through the introduction of SQDs, and the subsequent formatio
streptavidin noncovalent bonds with the microtubules. Mechanical energy is
bending of the microtubule filaments, as well as the formation of coiled co
domains within the assembled structures.disassembly (breaking the components apart) of the composite
rings. Lastly, the formation of biotin–streptavidin noncovalent
bonds (18 kcal mol1)[21,22] constitutes the thermodynamic
component. In our system, the SQDs form biotin–streptavidin
bonds with multiple microtubules, which ultimately stabilize
the mechanical strain energy within the composites.
The nanocomposite rings are formed through a nonlinear
cyclic assembly/disassembly process as illustrated in Figure 2.
The dynamic nature of the composites was characterized by
determining the percentage of microtubules in nanocomposite
rings as a function of time. The assembly process was marked
by an initial stage of rapid assembly, a brief metastable stage at
12–15 min after addition of SQDs, and lastly a disassembly
stage (Fig. 2). Reassembly of the nanocomposite rings was not
observed following spontaneous disassembly. The assembly of
the nanocomposite rings is characterized by a nucleation and
growth process that is defined by the interaction of the energy-
dissipative and thermodynamic components. Figure 3 presents
a proposed scheme for the sequential nucleation and growth
events based on in-depth characterization of the structures by
electron microscopy and optical microscopy.
The first step in the nucleation of nanocomposite rings was
induced by the collision between two (or more) independent
Figure 2. Kin
nanocompos
interaction a
forces. The as
the system, a
metastable s
oligomeric co
and was depe
P< 0.03; 50%
(!), R2¼ 0.7
Adv. Mater. 2008, 20, 4476–4481
2008 WILEY-VCH Verlag GmbH & Coetics of nanocomposite assembly and disassembly. The
ite rings assemble/disassemble through a dynamic, nonlinear
mong energy-dissipating, thermodynamic, and mechanical
sembly stage occurred rapidly upon introduction of SQDs to
nd reached a maximum density at
15min. Following a brief
tage, the nanocomposite rings disassembled into linear
mposites. This process followed a cubic polynomial curve,
ndent on the level of biotinylated tubulin: 20% (), R2¼ 0.76,
(), R2¼ 0.89, P< 0.01; 70% (!), R2¼ 0.80, P< 0.01; 90%
9, P< 0.01.oligomers into a closed circular morphology. As stated above,
the large number of biotin–streptavidin bonds holding the
oligomer together compensated for the considerably high
levels of strain developed by the twisted and kinked domains in
these structures. The strain energy was also further partitioned
into the mechanical bending of the leading end of the oligomer,
forming oligomeric structures that were permanently or. KGaA, Weinheim www.advmat.de 4477

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4478transiently bent during translation (Fig. 3e and f). The strain-
induced curvature subsequently induced interactions between
the head and tail of oligomers, which linked the ends together
by biotin–streptavidin bonds (i.e., thermodynamic component)
Figure 3. Kinesin-based transport of SQD-laden microtubules resulted in
the formation of nanocomposite ring structures through a nucleation and
growth process. The initial stage of nucleation was marked by the for-
mation of oligomeric structures (a,b) that continued to be transported (and
rotated). The rotation of these oligomers resulted in the formation of
nanoscale coiled coil and kinked domains (c,d). While much of the
mechanical strain in these domains was compensated by the biotin–
streptavidin bonds, the strain energy also induced bending of the oligo-
mers (e,f) and drove the formation of a closed ring-like structure. The
direction of axial rotation in the oligomers dictated the direction of bending
and ultimately the rotational direction of the nanocomposite rings. Coun-
terclockwise rotating composites (g) resulted from populations with pre-
dominately counterclockwise rotation microtubules (14 protofilaments).
Conversely, clockwise rotating composites (h) resulted from populations
with predominately clockwise rotation microtubules (12 protofilaments).
The rotation of the composite enabled the incorporation of microtubules
upon contact, analogous to winding a spring (i). The nanocomposite rings
reached a metastable state around 15min after addition of SQDs (j–m).
www.advmat.de
2008 WILEY-VCH Verlag GmbH &and formed the closed nanocomposite rings. This step marked
the completion of the nucleation stage of the assembly process.
Once nucleated (i.e., closed rings were formed), the
composites continued to harvest mobile microtubules upon
contact, resulting in the overall growth of the structure. The
growth stage relied on the transport of SQD-coated micro-
tubules to the growing nanocomposite rings, as well as the
rotation of the nanocomposite rings to ‘‘wind up’’ the building
blocks into the composites (Fig. 3g–i). This process is
considerably different from ‘‘traditional’’ growth processes
in which diffusion drives the introduction of new building
blocks to a growing system and the subsequent thermodynamic
incorporation into the assembly. Initial results suggested that
the majority of the nanocomposite rings rotated in a counter-
clockwise manner. Based on the polymerization conditions, we
hypothesized that the rotational direction of the composites
directly correlated with the direction of axial rotation of the
microtubules. To test this hypothesis, we used different
experimental protocols to create microtubule populations that
were deliberately biased for counterclockwise or clockwise
rotation based on the number of protofilaments.[14,16] PIPES
buffer polymerized microtubules (majority with 14-protofila-
ments) and phosphate buffer polymerized microtubules
(majority with 12-protofilaments) were prepared as
described.[13,14] When counter-clockwise rotating microtubules
(14-protofilaments) dominated the distribution, the resulting
nanocomposite rings rotated predominantly (78%) in a
counter-clockwise direction (Fig. 3g; Supporting Information).
Conversely, a population containing a majority of clockwise
rotating microtubules (12 protofilaments) resulted in compo-
sites that rotated primarily clockwise (64%; Fig. 3h; Supporting
Information). The significant difference in rotation direction
with protofilament number (P< 0.001 in z-test) strongly
supports the role of axial rotation as the source of the
mechanical strain directing the bending of microtubules into
circular structures. Thus, the axial rotation played a significant
role in both dictating the direction of oligomer bending as well
as the rotational direction of the composites.
A metastable stage was observed at 12–15 min (Fig. 2) and
marked by the formation of interwoven ‘‘wreath-like’’
structures (Fig. 3j–m). This stage was marked phenomenolo-
gically by the dissipative contribution being restricted to
maintaining the rotation of the nanocomposite rings, and the
thermodynamic contribution providing the principal forces
stabilizing these organized ring structures. To demonstrate this
point, a nonhydrolyzable ATP analog, AMP-PNP, was added
to the system, and resulted in the cessation of the rotation (i.e.,
energy dissipation) but did not affect its structural integrity.
The distributions of inner and outer diameters and the
thickness of the composites at this stage are presented in
Figure 4. The inner diameters of the composites displayed an
exponential distribution (Fig. 4a), with an average diameter of
3.4 0.2mm (mean standard error of the mean). The non-
Gaussian distribution suggests that mechanical strain energy
and bending in the oligomers deterministically drive the rings
to form with a minimal inner diameter. To this point, theCo. KGaA, Weinheim Adv. Mater. 2008, 20, 4476–4481

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Nsmallest inner ring diameter was
1.2mm, which is consistent
with the radius of curvature at which microtubule break (i.e.,
0.6mm).[23] The outer diameter of the composites at this stage
exhibited a normal distribution (Fig. 4b) with an average
diameter of 5.2 0.2mm (mean standard error of the mean).
Similarly, the thickness of the ring composites was also
normally distributed (Fig. 4c), with an average thickness of
1.8 0.1mm (mean standard error of the mean). The
Gaussian distributions of the outer diameter and thickness
suggest that the ring growth occurs stochastically, which is
supported by the random nature of microtubule transport in
the inverted motility system. Overall, these data support the
Figure 4. Distributions of the inner (a) and outer (b) diameters and
thickness (c) of the ring-like composites.
Adv. Mater. 2008, 20, 4476–4481
2008 WILEY-VCH Verlproposed nucleation and growth process as the mechanism for
assembling the nanocomposite rings.
As stated above, the metastable rings represent a balance
between the elastic strain energy that accumulated by the
bending of the microtubules and the thermodynamic strength
built up from the bonds of biotin–streptavidin and kinesin–
microtubule. The structures are analogous to an elastic
‘‘nanospring’’ that stores considerable mechanical energy.
The elastic energy (U) stored within a typical nanocomposite
ring may be estimated by
X
Ui ¼
Xn
i¼1
2pk=ðDi þ naÞ (1)
where k is the flexural rigidity of a microtubule, a the sum of the
SQD and microtubule diameters (
40 nm), Di the inner
diameter of the composite, and n the estimated number of
coils. Based on the average inner and outer diameters (shown
above), the total stored elastic energy in a representative
composite is
33 000KBT (135 aJ).
Spontaneous disassembly began
15 min after addition of
SQDs (Fig. 2), and proceeded by autonomous ‘‘breakage’’ of
individual microtubules within the composites, and their
subsequent removal by nearby kinesin motors. We hypothesize
that localized, highly constrained defects and/or imperfections
in the ring geometry caused individual microtubules or
oligomers to break. The free ends of these microtubules
(oligomers) may readily interact with kinesin motors and be
stripped from the nanocomposite ring. The critical role of the
motors (i.e., energy dissipation) in disassembly was demon-
strated by adding AMP-PNP and inhibiting motor function.
Disassembly was not observed under these conditions, but was
initiated immediately following the addition of ATP back into
the system. Following disassembly, the microtubules were
shorter than the original linear microtubules (<5mm),
commonly bundled together, and unable to reassemble into
rings.
The nanocomposite rings could be reversibly disassembled
by controlling the degree of biotin–streptavidin stabilization
(Fig. 5). The addition of a gross excess (i.e., >104-fold excess)
of free biotin induced the rapid ‘‘unwinding’’ of the rotating
rings into individual linear microtubules. The mechanical
strain within the nanocomposite rings exerted a pulling force
on the biotin–streptavidin bonds, which affected the bond
strength[24] and off-rate of this noncovalent bond. The free
biotin also competed with the biotinylated tubulin for the
SQDs binding sites, reducing the thermodynamic input and
destabilizing the nanocomposite rings. Together, these two
effects resulted in the rapid disassembly of the composites.
Excess biotin alone, however, was not sufficient to drive the
disassembly. The nanocomposite rings were able to maintain
structural integrity when excess biotin was added to AMP-
PNP-immobilized rings, demonstrating a similar requirement
of energy-dissipation as was observed for spontaneous
disassembly. When these immobilized, biotin-treated ringsag GmbH & Co. KGaA, Weinheim www.advmat.de 4479

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4480were ‘‘turned on’’ by reactivating the kinesin with ATP, the
rings unwound into mobile, linear microtubules. The resulting
Figure 5. Kinetics of reversible disassembly. Addition of excess biotin to
rotating nanocomposite rings reduced the thermodynamic input (i.e.,
reduced the number of biotin–streptavidin bonds holding the composite
together), and induced the disassembly of the composites. The disas-
sembly followed an exponential rate (R2¼ 0.93, P< 0.001), reaching
complete disassembly within 15min. Photomicrographs are representative
of observations at t¼ 0, 5, and 15min. Scale bar¼ 5mm.linear microtubules were capable of reassembling upon
reintroduction of SQDs, confirming the reversibility of this
dynamic process.
In summary, we have described the mechanism governing
the dynamic self-assembly of nanocomposite rings through the
cooperative interaction of thermodynamic and energy-dis-
sipating processes. Assembly occurred in a highly parallel,
nonlinear manner, and led to the formation of mechanically
constrained structures capable of storing considerable elastic
energy. Spontaneous and reversible disassembly of these
structures was initiated by the intrinsically high level of
mechanical strain energy, and completed through energy-
dissipating transport. This system provides an enabling model
of how the collective behavior of energy-dissipating and
thermodynamic processes may be used to drive the dynamic
assembly of nanostructured composites. By understanding the
principles of dynamic self-assembly inspired by and involved
with biomolecular machinery, we envision the future devel-
opment of adaptive, ‘‘smart,’’ and reconfigurable materials
with wide range of applications, such as tunable microdevices,
sensors, control systems that are unconstrained by the
energetic limitations of passive self-assembly processes.
Experimental
Microtubule Polymerization: Biotinylated microtubules (0–100%
biotin) were polymerized by mixing biotinylated tubulin with
www.advmat.de
2008 WILEY-VCH Verlag GmbH &C ¼ ðMR MBÞARðMO MBÞAO
(2)
where MR is the mean fluorescence intensity of the ROI, MB is the
mean fluorescence intensity of auto-background, MO is the overall
mean fluorescence intensity of the field of view, AR is the area of ROI,
AO is the overall area of the field of view.
Electron Microscopy: STEM images were taken at JEOL 2010
high-resolution transmission electron microscope equipped with Gatan
slow scan charge-coupled device camera and operated at 200 keV.
Scanning electron microscopy (SEM) images were taken by Hitachi S-
450 SEM equipped with a field-emission gun. The MTs were directly
deposited on holey carbon grids (SPI Supplies) by incubating the grids
in solutions step by step. After complete ring formation, 1%
glutaraldehyde was used to fix the sample at room temperature for
30 min. After subsequent rinse with water, the sample was quick dry in
100% ethanol. Osmium oxide (2%) was used to stain the sample at
room temperature for 30 min. Samples were thoroughly rinsed with
water, dried, and imaged.
Received: May 10, 2008
Revised: May 10, 2008
[1] G. M. Whitesides, B. Grzybowski, Science 2002, 295, 2418.
[2] S. Camazine, J. Deneubourg, N. R. Franks, J. Sneyd, G. Theraulaz, E.
Bonabeau, Self-Organization in Biological Systems, Princeton Uni-
versity Press, Princeton 2003.
[3] G. Nicolis, I. Prigogine, Self-Organization in Nonequilibrium Systems:
From Dissipative Structures to Order Through Fluctuations, John
Wiley & Sons, New York 1977.
[4] A. Kurakin, Biosystems 2006, 84, 15.
[5] M. Fialkowski, K. J. M. Bishop, R. Klajn, S. K. Smoukov,
C. J. Campbell, B. A. Grzybowski, J. Phys. Chem. B 2006, 110, 2482.
[6] M. V. Sapozhnikov, I. S. Aranson, W. K. Kwok, Y. V. Tolmachev,
Phys. Rev. Lett. 2004, 93.
[7] B. A. Grzybowski, H. A. Stone, G. M. Whitesides, Nature 2000, 405,
1033.
[8] M. V. Sapozhnikov, Y. V. Tolmachev, I. S. Aranson, W. K. Kwok,
Phys. Rev. Lett. 2003, 90.
[9] D. J. Klingenberg, AICHE J. 2001, 47, 246.
[10] M. C. Cross, P. C. Hohenberg, Rev. Modern Phys. 1993, 65, 851.
[11] H. Hess, J. Clemmens, C. Brunner, R. Doot, S. Luna, K. H. Ernst, V.
Vogel, Nano Lett. 2005, 5, 629.fluorescent tubulin. PIPES-polymerized microtubules (majority 14-
protofilaments) were prepared as previously described [13]. Phosphate
buffer-polymerized microtubules (majority with 12-protofilaments)
[14] were prepared in 100 mM phosphate buffer (pH 7), 6 mM MgCl2,
1 mM GTP, and 2mM of paclitaxel and polymerized at 37 8C for 30 min.
Nanocomposite Assembly: Gliding motility assays were performed
at room temperature using a kinesin-1 from D. melanogaster and
published protocols [13]. Microtubules were diluted in motility solution
[13] supplemented with 4 mM ascorbic acid [25] to achieve a filament
density of 3 104/mm2. QDot 525 SQDs were diluted in motility
solution to provide concentrations of 0.2–100 nM. Solutions containing
1 mM AMP-PNP instead of 1 mM ATP, and 1 mM biotin were used in
reversible disassembly experiments.
Data Analysis: The circular regions were selected manually and the
background subtraction was performed with NI Vision auto threshold
function. The relative percentage of microtubules assembled into
nanocomposite rings (C) was estimated based on comparison of
background-adjusted, pixel-based fluorescence intensity of circular
versus noncircular regionsCo. KGaA, Weinheim Adv. Mater. 2008, 20, 4476–4481

C
O
M
M
U
N
IC
A
TIO
N
[12] C. Z. Dinu, J. Opitz, W. Pompe, J. Howard, M. Mertig, S. Diez, Small
2006, 2, 1090.
[13] M. Bachand, A. Trent, B. Bunker, G. Bachand, J. Nanosci. Nanotech.
2005, 5, 718.
[14] S. Ray, E. Meyhofer, R. A. Milligan, J. Howard, J. Cell Biol. 1993, 121,
1083.
[15] M. Kikumoto, M. Kurachi, V. Tosa, H. Tashiro, Biophys. J. 2006, 90,
1687.
[16] S. M. Block, Trends Cell Biol. 1995, 5, 169.
[17] L. Romberg, D. W. Pierce, R. D. Vale, J. Cell Biol. 1998, 140,
1407.
[18] D. L. Coy, M. Wagenbach, J. Howard, J. Biol. Chem. 1999, 274,
3667.
[19] G. D. Bachand, S. B. Rivera, A. K. Boal, J. Gaudioso, J. Liu, B. C.
Bunker, Nano Lett. 2004, 4, 817.
[20] R. D. Vale, B. J. Schnapp, T. S. Reese, M. P. Sheetz, Cell 1985, 40,
559.
[21] D. E. Hyre, I. Le Trong, E. A. Merritt, J. F. Eccleston, N. M. Green, R.
E. Stenkamp, P. S. Stayton, Protein Sci. 2006, 15, 459.
[22] G. O. Reznik, S. Vajda, T. Sano, C. R. Cantor, Proc. Natl. Acad. Sci.
USA 1998, 95, 13525.
[23] C. M. Waterman-Storer, E. D. Salmon, J. Cell Biol. 1997, 139, 417.
[24] R. Merkel, P. Nassoy, A. Leung, K. Ritchie, E. Evans, Nature 1999,
397, 50.
[25] H. Guo, C. Xu, C. Liu, E. Qu, M. Yuan, Z. Li, B. Cheng, D. Zhang,
Biophys. J. 2006, 90, 2093.Adv. Mater. 2008, 20, 4476–4481
2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.advmat.de 4481