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The self-assembly of block copolymers is often rationalized by structure and microphase separation; pathways that diverge from this parameter space may provide new mechanisms of polymer assembly. Here, we show that the sequence and length of single-stranded DNA directly influence the self-assembly of sequence-defined DNA block copolymers. While increasing the length of DNA led to predictable changes in self-assembly, changing only the sequence of DNA produced three distinct structures: spherical micelles (spherical nucleic acids, SNAs) from flexible poly(thymine) DNA, fibers from semirigid mixed-sequence DNA, and networked superstructures from rigid poly(adenine) DNA. The secondary structure of poly(adenine) DNA strands drives a temperature-dependent polymerization and assembly mechanism: copolymers stored in an SNA reservoir form fibers after thermal activation, which then aggregate upon cooling to form interwoven networks. DNA is often used as a programming code that aids in nanostructure addressability and function. Here, we show that the inherent physical and chemical properties of single-stranded DNA sequences also make them an ideal material to direct self-assembled morphologies and select for new methods of supramolecular polymerization.
DNA Sequence and Length Dictate the Assembly of Nucleic Acid
Block Copolymers
Felix J. Rizzuto,*
,§
Michael D. Dore,
§
Muhammad Ghufran Raque, Xin Luo, and Hanadi F. Sleiman*
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ABSTRACT: The self-assembly of block copolymers is often rationalized
by structure and microphase separation; pathways that diverge from this
parameter space may provide new mechanisms of polymer assembly. Here,
we show that the sequence and length of single-stranded DNA directly
inuence the self-assembly of sequence-dened DNA block copolymers.
While increasing the length of DNA led to predictable changes in self-
assembly, changing only the sequence of DNA produced three distinct
structures: spherical micelles (spherical nucleic acids, SNAs) from exible
poly(thymine) DNA, bers from semirigid mixed-sequence DNA, and
networked superstructures from rigid poly(adenine) DNA. The secondary
structure of poly(adenine) DNA strands drives a temperature-dependent
polymerization and assembly mechanism: copolymers stored in an SNA
reservoir form bers after thermal activation, which then aggregate upon cooling to form interwoven networks. DNA is often used as
a programming code that aids in nanostructure addressability and function. Here, we show that the inherent physical and chemical
properties of single-stranded DNA sequences also make them an ideal material to direct self-assembled morphologies and select for
new methods of supramolecular polymerization.
INTRODUCTION
Sequence-dened DNA amphiphiles are covalent polymer
chains of monodisperse length and specic monomer order
attached to single-stranded DNA, constructed eciently and
rapidly on an automated DNA synthesizer.
110
Self-assembly
arises to minimize contact of the hydrophobic region with
water, and the relative volume of the hydrophobic to
hydrophilic block can play a major role in determining the
assembly morphology.
1113
Increasing the volume of the
hydrophobic phase generally decreases the interfacial curvature
(i.e., the curvature of the hydrophobic region at the interface
between the two blocks) evolving the morphology from
spheres to cylinders to lamellae.
14,15
In the case of DNA block
copolymerswhere DNA is the hydrophilic segment, attached
covalently to a block of hydrophobic monomersthis yields
supramolecular structures with DNA coronas that can be
addressed with functional moieties for numerous biological
and materials applications.
7,1620
Our group
3,9,2123
and others
24,25
have explored modulation
of the hydrophobic moietyits size, chemistry, and number of
repeat monomersin forming diverse structures, but rarely
has altering the hydrophilic DNA chain been investigated as a
driving force in self-assembly.
26,27
Single-stranded DNA
(ssDNA)chainsarenotalwaysdisorderedpolymers
electrostatics, πinteractions, and base hydrophobicity can
alter the conformation, rigidity, and internal structure of
ssDNA.
2833
Furthermore, intramolecular interactions be-
tween nonadjacent bases and phosphates on a single strand
of DNA may alter chain conguration, even transiently.
34,35
We hypothesized that increasing the local concentration of
DNA strands by enforcing their proximity in noncovalent
assemblies would organize these otherwise unstable inter-
molecular interactions, forming structured hydrophilic coronas
that directly aect self-assembly behavior.
Here, we investigate the inuence of the DNA chain
sequence and length in driving the morphology and self-
assembly mechanisms of DNA amphiphiles. All samples were
annealed in the presence of 12.5 mM Mg2+ at pH 8. In line
with the assembly principles of microphase separation, we
observe that increasing DNA length produces assemblies with
greater interfacial curvature. We observe that the sequence of
nucleobases within DNA strands plays a signicant role in
dictating the self-assembled structure. DNA chains of the same
length with dierent sequences produced dierent products: a
random sequence DNA amphiphile was observed to polymer-
ize into bers over the entire thermal trajectory; one composed
of only poly(adenine) residues was sequestered as a spherical
micelle and only activated for ber formation at a specic
Received: April 1, 2022
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temperature, and then formed hierarchical aggregates upon
cooling; while a third comprised of poly(thymine) was
retained as a spherical micelle robustly without ber formation
(Figure 1). The inherent supramolecular chemistriesthe
persistence length, exibility, and aromatic interactionsof
dierent sequences of DNA determine the morphology of their
resulting assemblies. Increasing the local concentration of these
interactions by packing into a polymer corona amplies these
Figure 1. DNA sequence and conformation is a prime determinant in driving amphiphile self-assembly. (a) When the DNA is a random sequence
(and thus semirigid), ber formation is observed as the hydrophobic tail (yellow) curls during heating; however, (b) when the DNA is exible
(polythymine, T19), only SNAs are observed. (c) When rigid DNA (polyadenine, A19) is employed, SNAs are initially formed. In this case, the
rigidity of the DNA strand prevents polymer reorganization into bers. Upon heating, the DNA melts to become more exible, facilitating ber
formation. Upon cooling, the now rigid DNA is capable of blunt end stacking with other bers. Color code: green, random DNA sequence; blue,
poly(thymine); orange, poly(adenine).
Figure 2. Varying the length of DNA dictates the morphology of resulting self-assembled architectures. (a) DNA amphiphiles with 12 C12 units
and nDNA bases assemble in the presence of Mg2+ to form (b) lamellae structures when n= 5, (c) bers when n= 19, and (d) spherical nucleic
acids (SNAs) when n= 33, as shown by AFM. Scale bars: 1 μm, 100 nm in insets.
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B
variations, driving the formation of networked superstructures
of bers.
RESULTS AND DISCUSSION
Changing DNA Length. We previously reported a DNA
amphiphile containing a covalent polymer with 12 branched
hydrophobic monomers (1,2-dodecanediol, C12) that are
punctuated by phosphates, and appended to a random
sequence of 19 DNA bases (C1212-DNA19,Figure 2a). This
amphiphile undergoes thermally driven supramolecular poly-
merization to form long, one-dimensional bers (Figures 1a
and 2c):
9
the hydrophobic block curls at elevated temperatures
to expose the phosphates and hide the C12 chains, promoting
fusion and ber elongation (Figure 1a).
9
By increasing the
length of the hydrophilic DNA segment, we expect the self-
assembly morphology to change following principles of
microphase separation: as the amphiphilic packing parameter
decreases, we expect assemblies with increasing interfacial
curvature.
15
Tuning the relative length of polymer blocks is an
ecient tool for controlling morphology: a size- and shape-
dened DNA nanostructure may be assembled from a single
molecular species, and each dierent morphology can inuence
cellular uptake and bioactivity properties.
36,37
Lengthening the DNA segment from 19 to 33 bases (C1212-
DNA33) resulted in the formation of spherical nucleic acids
(SNAs) (Figures 2d and S8). Dynamic light scattering (DLS)
revealed a diusion coecient (D) an order of magnitude
higher and less disperse than the bers formed by C1212-
DNA19 (Table S3), suggesting smaller, more uniform
structures that were conrmed by atomic force microscopy
(AFM) as SNAs (Figure 2d). Shortening the length of the
DNA segment to 5 nucleotide units (C1212-DNA5) gave
lamellar structures with sheet heights of 7.7 ±0.5 nm, as
observed by AFM (Figures 2b and S9) and reected in native
agarose gel electrophoresis (AGE, Figure S10). DLS gave
unstable high intensity signals due to the presence of large
aggregated assemblies. We were thus able to switch between
three unique polymer morphologies by varying the length of
the hydrophilic DNA segment alone from 5 to 33 bases
(Figure 2), highlighting the importance of length control in
DNA amphiphile self-assembly.
The sequence-specic addressability of the DNA corona
allowed us to construct hierarchical superstructures of C1212-
DNA19 bers using strand hybridization (Figure 3). When a
complement strand DNA19
was hybridized to bers of C1212-
DNA19 in solution, the ber corona became double stranded.
This process produced blunt ended DNA termini that
promoted π-interactions between bers, resulting in their
intermolecular association.
1
Micron-scale hierarchical struc-
tures were observed by AFM, composed of densely packed
supramolecular bers aligned parallel to one another (Figures
3a and S11). When a two thymidine overhang was added to
DNA19
andhybridizedtobers of C1212-DNA19,no
hierarchical structures were observed, as no blunt ends were
available for association (Figure S12). As a positive control, a
complement strand to DNA19 with a self-complementary GC
overhang was added to C1212-DNA19 and hierarchical
structures of aligned bers were observed, with a similar
morphology and interber distance to that of the no-overhang
case (Figures S13 and 14). Blunt end stacks can thus be used
to control the hierarchical assembly of our addressable DNA
bers. Similar materials are common in biological contexts
such as muscle bers or the extracellular matrix, where
organized supramolecular polymers provide mechanical
function and specic motifs for interacting with cells.
Changing DNA Sequence. We observed that simply
changing the sequence of the DNA block, without changing
the length of the chain, could alter the self-assembly behavior
of our DNA amphiphiles (Figure 1). Our 19mer DNA
amphiphile C1212-DNA19 was designed as a random sequence
with a 5mer thymidine connector proximal to the hydrophobic
chains. This amphiphile forms bers at all annealing temper-
atures as observed by AGE (Figure S18). Replacing the
hydrophilic segment with a 19mer poly(thymine) sequence did
not produce bers when heated up to 90 °C; only spherical
micelles were observed by AGE and AFM (Figure 4). In
Figure 3. Hierarchical assembly from DNA strand hybridization. (a)
When hybridized to a full complement strand DNA19
,bers of
C1212-DNA19 aggregate parallel to one another, forming hierarchical
superstructures, (b) as observed by AFM. Scale bars: 500 nm.
Figure 4. Switching from a random DNA sequence to a poly-
(thymine) tail forms SNAs, when bers were predicted. (a) C1212-T19
forms only SNAs regardless of the heating conditions, as shown by
(b) native agarose gel electrophoresis (AGE, 1xTAMg buer). (c)
AFM of a sample heated to 90 °C. Scale bar: 1 μm.
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C
contrast to random DNA sequence C1212-DNA19 bers and
C1212-T19 spheres, C1212-A19wherein the DNA sequence is
poly(adenine)formed SNAs at room temperature, and only
formed bers when annealed above 60 °C(SI Section 7).
These three distinct assembly behaviorsall using the same
length of DNAsuggest that the choice of nucleobase aects
the amphiphiles self-assembly. The precise structures formed,
however, appear counterintuitive: adenine is larger than
thymine, such that the volume of a poly(dA) strand should
be larger than that of a poly(dT) strand of equal length, yet we
observe assemblies with greater interfacial curvature of
poly(dT), as compared to poly(dA). Thymidine is also more
hydrophobic than adenosine,
28
which should evolve the
assembly further, rather than closer, to a spherical morphology.
Crucially important, however, is that the persistence length of
single-stranded DNA varies greatly with nucleotide number
and sequence:
38
for example, a poly(dA) sequence has a higher
persistence length than poly(dT), owing to the presence of
base stacking interactions between purine basesit presents as
a rigid, structured helix, akin to double-stranded B-DNA.
3942
We propose that this higher conformational freedom for
poly(dT) produces hydrophilic blocks with a larger volume,
proximal to the hydrophobic core for C1212-T19; whereas in
C1212-A19 these hydrophilic DNA blocks are more rigid and
elongated, reducing interfacial curvature between blocks and
promoting their polymerization. A random DNA sequence
which incorporates a mixture of pyrimidines and purineshas
an intermediate persistence length between the extremes of
rigid A19 (purine only) and exible T19 (pyrimidine only).
Despite being all DNA, poly(dA), poly(dT), and a random
sequence are analogous to three dierent hydrophilic polymers
Figure 5. Switching the hydrophilic tail to a poly(dA) sequence forms hierarchical ber aggregates due to corona dis- and reordering. (a) Our DNA
amphiphile C1212-A19 self-assembles into (i) spherical micelles upon the addition of Mg2+. (ii) Upon heating to 60 °C, ber polymerization is
initiated abruptly. (iii) Upon cooling, the poly(dA) strands behave like structured helices. (iv) The blunt end termini of these bers assemble into
aggregates. These temperature-activated assemblies are due to conformational dierences of the poly(dA) strands, which are shown as cartoon
insets throughout (a). (b) AFM image of SNAs formed at RT (scale bar = 1 μm; inset scale bar = 100 nm), compared to (c) AFM images of
dierent aggregate morphologies observed during rapid cooling (left), as opposed to slow cooling (right). Scale bars = 1 μm; inset scale bars = 200
nm. For insets, scale bars are 100 nm for b. (d) Native AGE (1xTAMg buer) showing the initiation of polymerization at 60 °C, and the
hierarchical aggregates thus formed. (e) Variable temperature UVvis spectroscopy following the absorbance at 258 nm during heating to form our
bers (black) and cooling to form aggregate structures (red). (f) These aggregates melt over a broad temperature range starting at 45 °C, and
reform with a hysteresis of ca. 14 °C, as measured by UVvis spectroscopy. This melting graph is similar to that observed for poly(dA) strands
without hydrophobic attachments (Figure S33).
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D
with diering rigidity, translating into three unique assembly
behaviors.
The polymerization of C1212-A19 into bers was activated
abruptly at 60 °C, as discerned by AFM (Figure 5b,c), AGE
(Figure 5d), and UV spectra (Figure 5e). By variable
temperature UV spectroscopy, we observed the appearance
of broad spectral bands at >260 nm past 60 °C, corresponding
to the Rayleigh scattering of our thermoset supramolecular
polymers formed in situ (Figure S30). Concurrently, we
observed a sharp hyperchromicity of the band at 260 nm,
accompanied by a decrease in the intensity of all CD bands
with increasing temperature (Figure S32). Poly(dA) exists as a
structured helix at room temperature;
43
thus our spectroscopic
data indicate that stacking interactions between adjacent
adenine residues break upon heating, suggesting that the
secondary structure of the poly(dA) collapses upon heating
and ber formation. Due to the rigid and persistent hold at
room temperature, we thus propose that the adenine chains
kinetically trap the morphology into a spherical micelle and
prevent ber formation, which requires reorganization and
curling of the hydrophobic chains to align on top of one
another (Figure 1). At 60 °C, the melting of the adenine stacks
brings enough conformational freedom to allow rearrangement
of the hydrophobic block and subsequent polymerization into
brous architectures (Figure 5a).
Upon cooling, our C1212-A19 bers aggregate into
hierarchical superstructures (Figures 5), whereas C1212-
DNA19 is observed as individual long bers by AFM.
9
The
assembly of C1212-A19 into superstructures occurs upon
cooling in the range 6050 °C, as shown by hypochromicity
in the UVvis spectra (Figure 5e). The rate of cooling was
observed to signicantly aect the resulting morphology:
Single bers, two or three bers in parallel, and starburst ber
structures resulted from rapid cooling (50 °C min1), whereas
slow cooling at 0.2 °C min1resulted in large, interwoven, and
threaded architectures, as observed by AFM and TEM
(Figures 5c and 6). Commensurate with a slow reassembly
mechanism, a large hysteresis (ca. 14 °C) was observed
between assembly and disassembly of these superstructures by
UVvis spectroscopy (Figure 5f). The morphology of these
superstructures, in which individual bers prefer to align
parallel to one another (Figure 6), suggest that the DNA
corona is directing self-assembly upon cooling.
We hypothesize that both our temperature-specic polymer-
ization and hierarchical aggregates for C1212-A19 are a result of
the adenineadenine interactions within and between the
DNA chains. Unique among the DNA bases, poly(adenine)
strands exist as structured helices in solution, owing to
nucleobase high aromatic surface areas, penchant for ππ
stacking and self-complementary hydrogen bonding.
32,39
These
interactions break apart upon heating, which may lead to less
structured DNA coronas that allow the conversion of
kinetically trapped SNAs into bers (Figure 5aiii). Upon
cooling, these intramolecular interactions are restabilized:
Extended πsurfaces form at the corona-solvent boundary
from a combination of the rigid, π-stacked individual poly(dA)
strands and dynamic blunt end termini between DNA strands,
resulting in superstructures (Figures 5aiiiiv and 6) in a similar
manner to the double-stranded blunt end amphiphile in Figure
3. The increased local concentration of poly(dA) strands
within the ber coronas may enhance interchain association by
hydrogen bonding (adenine is self-complementary) and/or π-
stacking, generating analogous parallel structures with dynamic
blunt end termini.
Single-stranded poly(adenine) DNA is mostly in the C2-
endo or B-DNA form, with a minor contribution of the C3-
endo or A-DNA form.
32,44
The largest contributor to the A-
form in a typical d(A)nstrand is the 3-end residue which has
the greatest conformational mobility, as compared to the more
rigid internal adenines and 5-end. In the circular dichroism
(CD) spectrum of poly(dA), a positive band at 270 nm
indicates the B- vs A-DNA ratio: the smaller it is, the lower the
A-DNA contribution.
44
Thus, the CD band at 270 nm can also
indicate the extent of the conformational mobility of the 3-
endthe smaller the band, the more rigid the 3-end, resulting
in a lower A-DNA contribution. Upon assembly of C1212-A19
into the SNA and ber states, the positive CD band at 270 nm
diminishes, suggesting that, in these nanostructures, the
adenine chains are more B-DNA-like (Figure S32). This
supports reduced conformational mobility of the 3-end of
poly(dA) sequences in the nanostructures, which lie at the
coronawater interface. This more rigid interface in the SNA
state can provide an energy barrier to chain rearrangement and
ber formation that is absent in other DNA sequences of the
same length. Once the bers are formed, this rigid corona
solvent interface can result in stronger blunt end interactions
and ber aggregation.
When a complementary DNA strand with a 2T overhang
was hybridized to bers of C1212-DNA19, we observed that no
interber aggregation occurred (Figure S12). To further
investigate our hypothesis of adenineadenine base stacking
interactions in C1212-A19, we capped the 3terminus of the A19
strand with two thymidine monomers (C1212-A19T2).
Polymerization to form bers occurred over all temperature
ranges as observed by AGE (Figure S35) without the
formation of kinetically trapped SNAs. Fibers were signicantly
shorter that those of C1212-A19 and few hierarchical aggregates
were observed by AFM (Figure S36), suggesting that the
presence of adenine nucleobases at the solventcorona
boundary was critical for temperature-activated polymer-
ization. It is possible that the 2T overhang folds back onto
the A19 strands, thus reducing adenineadenine interactions
and decreasing strand rigidity at the 3-strand ends, which
reside at the solventcorona boundary. That C1212-A19T2
does not form aggregate superstructures akin to C1212-A19
further suggests that blunt end stacking, rather than interber
hybridization, is responsible for their hierarchical assembly.
We further explored the rigidity of our DNA constructs by
adding Hoechsts dye 33342 (Figure 7), a small molecule
Figure 6. TEM images of aggregates of C1212A20 bers. Interber
distances were calculated to be 12.9 ±1.4 nm, consistent with
proximal ππstacking between bers. Scale bars = 200 nm.
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E
known to bind to the minor groove of double-stranded DNA,
producing a positive induced CD (ICD) signal at ca. 360 nm.
45
In both the SNA and ber states of C1212-A19 this ICD signal
was enhanced as compared to free A19, suggesting improved
binding of the dye in these assembled states (Figure 7a). In
contrast, no ICD signal for C1212-T19 was observed, consistent
with the greater rigidity and B-DNA character of C1212-A19
(Figure 7b). Upon heating the C1212-A19 SNAs, the ICD
spectrum shifted from one dominated by interdye charge
transfer (20 40 °C), to one dominated by o-resonance
dye-DNA exciton coupling (40 60 °C), and nally
unbinding of the dye (at >60 °C) (Figure S37).
46
These
spectral progressions indicate conformational changes occur-
ring in the poly(dA) corona upon heating. Held rigid in the
SNA state, the DNA strands melt upon heating, breaking
intramolecular adenineadenine interactions that disorganize
the SNA corona, leading to unbinding of the dye as the DNA
strand approaches a less structured state.
Our data suggest that our C1212-A19 SNAs act as reservoirs
that rst store single amphiphile chains and subsequently
release them for polymerization following DNA melting. Two
forces compete at elevated temperature: As the poly(dA)
corona becomes less structured, the thermosetting core
cements at the same time. When the corona becomes more
dynamic at higher temperature, rearrangement of the hydro-
phobic strands to a curled conformation is enabled, promoting
core fusion and ber formation. The SNA corona thus
provides an additional activation barrier to polymerization.
Increasing temperature overcomes the π-stacking of poly-
(adenine) strands, allowing their conformations to approx-
imate that of random DNA at elevated temperatures, enabling
ber formation (Figure 5a).
This polymerization mechanism can override the morphol-
ogy predicted by microphase separation. A 30mer of poly(dA)
attached to 12 C12 units C1212-A30 formed rst SNAs at room
temperature, followed by the formation of bers upon heating
past 70 °C(Figures 8 and S43), in the same manner as C1212-
A19. This activation temperature is slightly higher than that for
the shorter A19 sequence, commensurate with the greater
degree of thermal stability expected for longer lengths of DNA.
C1212-A30 bers also formed hierarchical aggregates depending
on their length and rate of cooling. Longer bers produced
micron-length clumpy aggregates when cooled rapidly; they
formed extended aggregates when cooled slowly (Figure 8,
right). We expected an A30 corona to produce SNAs
exclusively (in line with the assembly of the random sequence
33mer C1212-DNA33 shown in Figure 2). The deviation from
an SNA structure at elevated temperature is commensurate
with the thermal activation of the DNA strands for ber
formation; upon cooling, the corresponding increase in rigidity
Figure 7. CD spectra of ssDNA and corresponding assemblies with
C1212 appended, all in the presence of Hoeschts dye (where single
stranded DNA is black, SNAs are red and bers are blue). (a) ssA19
DNA compared to C1212-A19 SNAs and bers; (b) ssT19 DNA
compared to C1212-T19 SNAs; and (c) ssDNA19 compared to C1212-
DNA19 bers. Notably, only assemblies from (a) and (c) showed
evidence of interactions with the dye.
Figure 8. Fiber formation using C1212-A30 and its hierarchical assembly. C1212-A30 polymerized under the same mechanism as C1212-A19, forming
spherical micelles up to a specic annealing temperature, over which bers were formed, which aggregated into superstructures upon cooling. Scale
bares: 500 nm.
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F
of the poly(dA) strands reforms the structured poly(A) helices,
forming networked aggregates.
CONCLUSIONS
The morphology and pathway complexity of self-assembled
DNA amphiphiles cannot be predicted by the length of the
hydrophilic DNA chain alone. Progressively increasing the
length of a random sequence DNA block changed the resultant
morphology from sheets to bers to spheres; as expected from
changes in the amphiphile packing parameter. In contrast,
changing only the sequence of DNA had unexpected impacts on
the self-assembly. Dierent morphologies were observed for
the same length of DNA with dierent sequencesspheres for
T19,bers for random sequence DNA19 and networked bers
for A19due to dierences in their single-stranded con-
formations. While bers were formed at all temperatures for
random sequence DNA19 amphiphiles, A19 amphiphiles rst
assembled into kinetically trapped spherical micelles, and only
produced bers upon thermal denaturation of their structured
poly(dA) corona. The assembly pathways were also aected by
interpolymer chainchain interactions and the solventcorona
interface, driving the assembly of hierarchical superstructures.
Resembling biological tissues such as tendon and extracellular
matrices, these superstructures consisted of densely packed
supramolecular bers that may nd applications in tissue
engineering and delivery.
DNA self-assembly in biology and nanotechnology is
fundamentally dictated by sequence. In this work we have
extended the role of DNA sequence beyond the typical
paradigm of complementarity, embracing the chemical and
physical properties of specic single-stranded DNA sequences
to dictate polymerization and assembly pathways. The results
show that dierent sequences of DNA can act like blocks of
dierent hydrophilic polymers both within, and diverging from,
the simple principles of amphiphilic block copolymer self-
assembly. The potential to replace other hydrophilic polymers
with dierent sequences of DNA may allow improvements in
biocompatibility and therapeutic function of many block
copolymer systems. Understanding and developing new corona
interactions using DNA amphiphiles could additionally unlock
the potential of DNA-minimal structures for new hierarchical
assemblies that proer sensing, diagnostic, and drug delivery
applications. Future work will expand upon the sequence
diversity of DNA within our block copolymers, with the goal of
programming individual sequences to be activated for
polymerization at specic temperatures.
ASSOCIATED CONTENT
*
sıSupporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.2c03506.
Synthesis details, additional AFM, AGE, TEM, UVvis,
CD, and LC-MS data. (PDF)
AUTHOR INFORMATION
Corresponding Authors
Felix J. Rizzuto Department of Chemistry, McGill
University, Montréal QC H3A 08B, Canada; Present
Address: School of Chemistry, University of New South
Wales, Sydney, 2052, Australia;orcid.org/0000-0003-
2799-903X; Email: f.rizzuto@unsw.edu.au
Hanadi F. Sleiman Department of Chemistry, McGill
University, Montréal QC H3A 08B, Canada; orcid.org/
0000-0002-5100-0532; Email: hanadi.sleiman@mcgill.ca
Authors
Michael D. Dore Department of Chemistry, McGill
University, Montréal QC H3A 08B, Canada
Muhammad Ghufran Raque Department of Chemistry,
McGill University, Montréal QC H3A 08B, Canada
Xin Luo Department of Chemistry, McGill University,
Montréal QC H3A 08B, Canada
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.2c03506
Author Contributions
§
F.J.R. and M.D.D. contributed equally.
Notes
The authors declare no competing nancial interest.
ACKNOWLEDGMENTS
F.J.R. thanks the National Science and Engineering Research
Council of Canada (NSERC) for a Banting Fellowship and the
Australian Research Council (ARC) for a Discovery Early
Career Research Award (DECRA). M.G.R. thanks the NSERC
for a Vanier Scholarship and the Fonds de Recherche Nature
et Technologies (FRQNT) for a Doctoral Research Scholar-
ship. H.F.S. is thankful to NSERC, the Canada Foundation for
Innovation (CFI) and the FRQNT. H.F.S. is also thankful to
the Canada Research Chairs Program, the Canada Council for
the Arts for a Killam Fellowship and is a Cottrell Scholar of the
Research Corporation.
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