Editing Self-assembly (section)

== In chemistry and materials science ==
{{main|Molecular self-assembly}}
[[File:DNA nanostructures.png|thumb|upright=1.2|The [[DNA]] structure at left ([[schematic]] shown) will self-assemble into the structure visualized by [[Atomic force microscope|atomic force microscopy]] at right.]]
Self-assembly in the classic sense can be defined as ''the spontaneous and [[Reversible reaction|reversible]] organization of molecular units into ordered structures by [[non-covalent interactions]]''. The first property of a self-assembled system that this definition suggests is the [[Emergence#Emergent properties and processes|spontaneity]] of the self-assembly process: the interactions responsible for the formation of the self-assembled system act on a strictly local level—in other words, ''the [[nanostructure]] builds itself''.

Although self-assembly typically occurs between weakly-interacting species, this organization may be transferred into strongly-bound [[covalent]] systems. An example for this may be observed in the self-assembly of [[polyoxometalate]]s. Evidence suggests that such molecules assemble via a dense-phase type [[Reaction mechanism|mechanism]] whereby small oxometalate ions first [[Molecular self-assembly|assemble non-covalently]] in solution, followed by a [[condensation reaction]] that covalently binds the assembled units.<ref>{{cite journal | vauthors = Schreiber RE, Avram L, Neumann R | title = Self-Assembly through Noncovalent Preorganization of Reactants: Explaining the Formation of a Polyfluoroxometalate | journal = Chemistry: A European Journal | volume = 24 | issue = 2 | pages = 369–379 | date = January 2018 | pmid = 29064591 | doi = 10.1002/chem.201704287 }}</ref> This process can be aided by the introduction of templating agents to control the formed species.<ref>{{cite journal | vauthors = Miras HN, Cooper GJ, Long DL, Bögge H, Müller A, Streb C, Cronin L | title = Unveiling the transient template in the self-assembly of a molecular oxide nanowheel | journal = Science | volume = 327 | issue = 5961 | pages = 72–4 | date = January 2010 | pmid = 20044572 | doi = 10.1126/science.1181735 | bibcode = 2010Sci...327...72M | s2cid = 24736211 }}</ref> In such a way, highly organized covalent molecules may be formed in a specific manner.

Self-assembled nano-structure is an object that appears as a result of ordering and aggregation of individual nano-scale objects guided by some [[physics|physical]] principle.

A particularly counter-intuitive example of a physical principle that can drive self-assembly is [[entropy]] maximization. Though entropy is conventionally [[entropy (order and disorder)|associated with disorder]], under suitable conditions <ref name="vanAndersPNAS2014"/> entropy can drive nano-scale objects to self-assemble into target structures in a controllable way.<ref name="Engineering entropy for the inverse">{{cite journal | vauthors = Geng Y, van Anders G, Dodd PM, Dshemuchadse J, Glotzer SC | title = Engineering entropy for the inverse design of colloidal crystals from hard shapes | journal = Science Advances | volume = 5 | issue = 7 | pages = eaaw0514 | date = July 2019 | pmid = 31281885 | pmc = 6611692 | doi = 10.1126/sciadv.aaw0514 | arxiv = 1712.02471 | bibcode = 2019SciA....5..514G }}</ref>

Another important class of self-assembly is field-directed assembly. An example of this is the phenomenon of electrostatic trapping. In this case an [[electric field]] is applied between two metallic nano-electrodes. The particles present in the environment are polarized by the applied electric field. Because of dipole interaction with the electric field gradient the particles are attracted to the gap between the electrodes.<ref>{{cite journal| vauthors = Bezryadin A, Westervelt RM, Tinkham M |title=Self-assembled chains of graphitized carbon nanoparticles|journal=Applied Physics Letters|date=1999|doi=10.1063/1.123941|volume=74|issue=18|pages=2699–2701|arxiv=cond-mat/9810235|bibcode=1999ApPhL..74.2699B|s2cid=14398155}}</ref> Generalizations of this type approach involving different types of fields, e.g., using magnetic fields, using capillary interactions for particles trapped at interfaces, elastic interactions for particles suspended in liquid crystals have also been reported.

Regardless of the mechanism driving self-assembly, people take self-assembly approaches to materials synthesis to avoid the problem of having to construct materials one building block at a time. Avoiding one-at-a-time approaches is important because the amount of time required to place building blocks into a target structure is prohibitively difficult for structures that have macroscopic size.

Once materials of macroscopic size can be self-assembled, those materials can find use in many applications. For example, nano-structures such as nano-vacuum gaps are used for storing energy<ref>{{cite journal| vauthors = Lyon D, Hubler A |title=Gap size dependence of the dielectric strength in nano vacuum gaps|journal=IEEE Transactions on Dielectrics and Electrical Insulation|date=2013|doi=10.1109/TDEI.2013.6571470|volume=20|issue=4|pages=1467–1471|s2cid=709782}}</ref> and nuclear energy conversion.<ref>{{cite journal| vauthors = Shinn E |title=Nuclear energy conversion with stacks of graphene nanocapacitors |journal=Complexity|date=2012|doi=10.1002/cplx.21427|volume=18|issue=3|pages=24–27|bibcode=2013Cmplx..18c..24S}}</ref> Self-assembled [[tunable metamaterial|tunable materials]] are promising candidates for large surface area electrodes in [[Battery (electricity)|batteries]] and organic photovoltaic cells, as well as for microfluidic sensors and filters.<ref>{{cite journal | vauthors = Demortière A, Snezhko A, Sapozhnikov MV, Becker N, Proslier T, Aranson IS | title = Self-assembled tunable networks of sticky colloidal particles | journal = Nature Communications | volume = 5 | pages = 3117 | date = 2014 | pmid = 24445324 | doi = 10.1038/ncomms4117 | doi-access = free | bibcode = 2014NatCo...5.3117D }}</ref>

=== Distinctive features ===
At this point, one may argue that any chemical reaction driving atoms and molecules to assemble into larger structures, such as [[precipitation (chemistry)|precipitation]], could fall into the category of self-assembly. However, there are at least three distinctive features that make self-assembly a distinct concept.

==== Order ====
First, the self-assembled structure must have a higher [[Order (crystal lattice)|order]] than the isolated components, be it a shape or a particular task that the self-assembled entity may perform. This is generally not true in [[chemical reaction]]s, where an ordered state may proceed towards a disordered state depending on thermodynamic parameters.

==== Interactions ====
The second important aspect of self-assembly is the predominant role of weak interactions (e.g. [[Van der Waals force|Van der Waals]], [[capillary action|capillary]], [[Pi-pi interaction|<math>\pi-\pi</math>]], [[hydrogen bond]]s, or [[entropic force#Colloids|entropic forces]]) compared to more "traditional" covalent, [[ionic bond|ionic]], or [[metallic bond]]s. These weak interactions are important in materials synthesis for two reasons.

First, weak interactions take a prominent place in materials, especially in biological systems. For instance, they determine the physical properties of liquids, the [[solubility]] of solids, and the organization of molecules in biological membranes.<ref>{{cite book| vauthors = Israelachvili JN |title=Intermolecular and Surface Forces|edition=3rd|publisher=Elsevier|year=2011}}</ref>

Second, in addition to the strength of the interactions, interactions with varying degrees of specificity can control self-assembly. Self-assembly that is mediated by DNA pairing interactions constitutes the interactions of the highest specificity that have been used to drive self-assembly.<ref>{{cite journal | vauthors = Jones MR, Seeman NC, Mirkin CA | title = Nanomaterials. Programmable materials and the nature of the DNA bond | journal = Science | volume = 347 | issue = 6224 | pages = 1260901 | date = February 2015 | pmid = 25700524 | doi = 10.1126/science.1260901 | doi-access = free }}</ref> At the other extreme, the least specific interactions are possibly those provided by [[entropic force#Colloids|
emergent forces that arise from entropy maximization]].<ref name="vanAndersPNAS2014">{{cite journal | vauthors = van Anders G, Klotsa D, Ahmed NK, Engel M, Glotzer SC | title = Understanding shape entropy through local dense packing | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 45 | pages = E4812-21 | date = November 2014 | pmid = 25344532 | pmc = 4234574 | doi = 10.1073/pnas.1418159111 | arxiv = 1309.1187 | bibcode = 2014PNAS..111E4812V | doi-access = free }}</ref>

==== Building blocks ====
The third distinctive feature of self-assembly is that the building blocks are not only atoms and molecules, but span a wide range of nano- and [[mesoscopic]] structures, with different chemical compositions, functionalities,<ref name="Anisotropy of building blocks and t">{{cite journal | vauthors = Glotzer SC, Solomon MJ | title = Anisotropy of building blocks and their assembly into complex structures | journal = Nature Materials | volume = 6 | issue = 8 | pages = 557–62 | date = August 2007 | pmid = 17667968 | doi = 10.1038/nmat1949 | bibcode = 2007NatMa...6..557G }}</ref> and shapes.<ref>{{cite journal | vauthors = van Anders G, Ahmed NK, Smith R, Engel M, Glotzer SC | title = Entropically patchy particles: engineering valence through shape entropy | journal = ACS Nano | volume = 8 | issue = 1 | pages = 931–40 | date = January 2014 | pmid = 24359081 | doi = 10.1021/nn4057353 | arxiv = 1304.7545 | s2cid = 9669569 }}</ref>{{Anchor|shapes2016-01-29}} <ref name=Mayorga>{{cite journal |last1=Mayorga |first1=Luis S. |last2=Masone |first2=Diego |title=The Secret Ballet Inside Multivesicular Bodies |journal=ACS Nano |date=2024 |volume=18 |issue=24 |pages=15651–15660 |doi=10.1021/acsnano.4c01590|pmid=38830824 }}</ref> Research into possible three-dimensional shapes of self-assembling micrites examines [[Platonic solids]] (regular polyhedral).  The term 'micrite' was created by [[DARPA]] to refer to sub-millimeter sized [[Microrobotics|microrobots]], whose self-organizing abilities may be compared with those of [[slime mold]].<ref>{{cite journal| vauthors = Solem JC |year=2002|title=Self-assembling micrites based on the Platonic solids|journal=Robotics and Autonomous Systems|volume=38|issue=2|pages=69–92 |doi=10.1016/s0921-8890(01)00167-1|url=https://zenodo.org/record/1260141}}</ref><ref>{{cite journal| vauthors = Trewhella J, Solem JC |year=1998|title=Future Research Directions for Los Alamos: A Perspective from the Los Alamos Fellows |journal=Los Alamos National Laboratory Report LA-UR-02-7722|pages=9 |url=http://www.lanl.gov/collaboration/fellows/_assets/papers/future-research-directions-la-ur-02-7722.pdf}}</ref> Recent examples of novel building blocks include [[tetrahedron packing|polyhedra]] and [[patchy particles]].<ref name="Anisotropy of building blocks and t"/> Examples also included microparticles with complex geometries, such as hemispherical,<ref>{{cite journal | vauthors = Hosein ID, Liddell CM | title = Convectively assembled nonspherical mushroom cap-based colloidal crystals | journal = Langmuir | volume = 23 | issue = 17 | pages = 8810–4 | date = August 2007 | pmid = 17630788 | doi = 10.1021/la700865t }}</ref> dimer,<ref name="Hosein 10479–10485">{{cite journal | vauthors = Hosein ID, Liddell CM | title = Convectively assembled asymmetric dimer-based colloidal crystals | journal = Langmuir | volume = 23 | issue = 21 | pages = 10479–85 | date = October 2007 | pmid = 17629310 | doi = 10.1021/la7007254 | author2-link = Chekesha Liddell }}</ref> discs,<ref>{{cite journal | vauthors = Lee JA, Meng L, Norris DJ, Scriven LE, Tsapatsis M | title = Colloidal crystal layers of hexagonal nanoplates by convective assembly | journal = Langmuir | volume = 22 | issue = 12 | pages = 5217–9 | date = June 2006 | pmid = 16732640 | doi = 10.1021/la0601206 }}</ref> rods, molecules, as well as multimers. These nanoscale building blocks can in turn be synthesized through conventional chemical routes or by other self-assembly strategies such as [[Entropic force#Colloids|directional entropic forces]]. More recently, inverse design approaches have appeared where it is possible to fix a target self-assembled behavior, and determine an appropriate building block that will realize that behavior.<ref name="Engineering entropy for the inverse"/>

=== Thermodynamics and kinetics ===
Self-assembly in microscopic systems usually starts from diffusion, followed by the nucleation of seeds, subsequent growth of the seeds, and ends at [[Ostwald ripening]]. The thermodynamic driving free energy can be either [[enthalpic]] or [[entropic]] or both.<ref name="vanAndersPNAS2014"/> In either the enthalpic or entropic case, self-assembly proceeds through the formation and breaking of bonds,<ref>{{cite journal | vauthors = Harper ES, van Anders G, Glotzer SC | title = The entropic bond in colloidal crystals | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 34 | pages = 16703–16710 | date = August 2019 | pmid = 31375631 | pmc = 6708323 | doi = 10.1073/pnas.1822092116 | bibcode = 2019PNAS..11616703H | doi-access = free }}</ref> possibly with non-traditional forms of mediation.
The kinetics of the self-assembly process is usually related to [[diffusion]], for which the absorption/adsorption rate often follows a [[Langmuir adsorption model]] which in the diffusion controlled concentration (relatively diluted solution) can be estimated by the [[Fick's laws of diffusion]]. The desorption rate is determined by the bond strength of the surface molecules/atoms with a thermal [[activation energy]] barrier. The growth rate is the competition between these two processes.

=== Examples ===
Important examples of self-assembly in materials science include the formation of molecular [[crystal]]s, [[colloid]]s, [[lipid bilayer]]s, [[phase-separated polymer]]s, and [[self-assembled monolayer]]s.<ref>{{cite journal | vauthors = Whitesides GM, Boncheva M | title = Beyond molecules: self-assembly of mesoscopic and macroscopic components | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 8 | pages = 4769–74 | date = April 2002 | pmid = 11959929 | pmc = 122665 | doi = 10.1073/pnas.082065899 | bibcode = 2002PNAS...99.4769W | doi-access = free }}</ref><ref name="whitesides_2005_science">{{cite journal | vauthors = Whitesides GM, Kriebel JK, Love JC | title = Molecular engineering of surfaces using self-assembled monolayers | journal = Science Progress | volume = 88 | issue = Pt 1 | pages = 17–48 | year = 2005 | pmid = 16372593 | doi = 10.3184/003685005783238462 | pmc = 10367539 | url = http://gmwgroup.harvard.edu/pubs/pdf/934.pdf | s2cid = 46367976 | citeseerx = 10.1.1.668.2591 | access-date = 2016-12-21 | archive-date = 2013-06-20 | archive-url = https://web.archive.org/web/20130620145149/http://gmwgroup.harvard.edu/pubs/pdf/934.pdf | url-status = dead }}</ref> The folding of polypeptide chains into proteins and the folding of nucleic acids into their functional forms are examples of self-assembled biological structures. Recently, the three-dimensional macroporous structure was prepared via self-assembly of diphenylalanine derivative under cryoconditions, the obtained material can find the application in the field of regenerative medicine or drug delivery system.<ref>{{cite journal | vauthors = Berillo D, Mattiasson B, Galaev IY, Kirsebom H | title = Formation of macroporous self-assembled hydrogels through cryogelation of Fmoc-Phe-Phe | journal = Journal of Colloid and Interface Science | volume = 368 | issue = 1 | pages = 226–30 | date = February 2012 | pmid = 22129632 | doi = 10.1016/j.jcis.2011.11.006 | bibcode = 2012JCIS..368..226B }}</ref> P. Chen et al. demonstrated a microscale self-assembly method using the air-liquid interface established by [[Faraday wave]] as a template. This self-assembly method can be used for generation of diverse sets of symmetrical and periodic patterns from microscale materials such as [[hydrogels]], cells, and cell spheroids.<ref>{{cite journal | vauthors = Chen P, Luo Z, Güven S, Tasoglu S, Ganesan AV, Weng A, Demirci U | title = Microscale assembly directed by liquid-based template | journal = Advanced Materials | volume = 26 | issue = 34 | pages = 5936–41 | date = September 2014 | pmid = 24956442 | pmc = 4159433 | doi = 10.1002/adma.201402079 | bibcode = 2014AdM....26.5936C }}</ref> Yasuga et al. demonstrated how fluid interfacial energy drives the emergence of three-dimensional periodic structures in micropillar scaffolds.<ref name="YasugaIseri2021">{{cite journal|last1=Yasuga|first1=Hiroki|last2=Iseri|first2=Emre|last3=Wei|first3=Xi|last4=Kaya|first4=Kerem|last5=Di Dio|first5=Giacomo|last6=Osaki|first6=Toshihisa|last7=Kamiya|first7=Koki|last8=Nikolakopoulou|first8=Polyxeni|last9=Buchmann|first9=Sebastian|last10=Sundin|first10=Johan|last11=Bagheri|first11=Shervin|last12=Takeuchi|first12=Shoji|last13=Herland|first13=Anna|last14=Miki|first14=Norihisa|last15=van der Wijngaart|first15=Wouter|title=Fluid interfacial energy drives the emergence of three-dimensional periodic structures in micropillar scaffolds|journal=Nature Physics|year=2021|volume=17|issue=7|pages=794–800|issn=1745-2473|doi=10.1038/s41567-021-01204-4|bibcode=2021NatPh..17..794Y|s2cid=233702358}}</ref> Myllymäki et al. demonstrated the formation of micelles, that undergo a change in morphology to fibers and eventually to spheres, all controlled by solvent change.<ref>{{cite journal | vauthors = Myllymäki TT, Yang H, Liljeström V, Kostiainen MA, Malho JM, Zhu XX, Ikkala O | title = Hydrogen bonding asymmetric star-shape derivative of bile acid leads to supramolecular fibrillar aggregates that wrap into micrometer spheres | journal = Soft Matter | volume = 12 | issue = 34 | pages = 7159–65 | date = September 2016 | pmid = 27491728 | pmc = 5322467 | doi = 10.1039/C6SM01329E | bibcode = 2016SMat...12.7159M | url = }}</ref>

=== Properties ===
Self-assembly extends the scope of chemistry aiming at [[chemical synthesis|synthesizing]] products with order and functionality properties, extending chemical bonds to weak interactions and encompassing the self-assembly of nanoscale building blocks at all length scales.<ref name="ozin_2005_nanochemistry">{{cite book| vauthors = Ozin GA, Arsenault AC |title=Nanochemistry: a chemical approach to nanomaterials|publisher=Cambridge: Royal Society of Chemistry|year= 2005|isbn=978-0-85404-664-5}}</ref> In covalent synthesis and polymerization, the scientist links atoms together in any desired conformation, which does not necessarily have to be the energetically most favoured position; self-assembling molecules, on the other hand, adopt a structure at the thermodynamic minimum, finding the best combination of interactions between subunits but not forming covalent bonds between them. In self-assembling structures, the scientist must predict this minimum, not merely place the atoms in the location desired.

Another characteristic common to nearly all self-assembled systems is their [[thermodynamic stability]]. For self-assembly to take place without intervention of external forces, the process must lead to a lower [[Gibbs free energy]], thus self-assembled structures are thermodynamically more stable than the single, unassembled components. A direct consequence is the general tendency of self-assembled structures to be relatively free of defects. An example is the formation of two-dimensional [[superlattice]]s composed of an orderly arrangement of micrometre-sized [[polymethylmethacrylate]] (PMMA) spheres, starting from a solution containing the microspheres, in which the solvent is allowed to evaporate slowly in suitable conditions. In this case, the driving force is capillary interaction, which originates from the deformation of the surface of a liquid caused by the presence of floating or submerged particles.<ref>{{cite journal | vauthors = Velev OD, Denkov ND, Kralchevsky PA, Ivanov IB, Yoshimura H, Nagayama K |doi=10.1021/la00048a054|title=Mechanism of formation of two-dimensional crystals from latex particles on substrates|year=1992 |journal=Langmuir |volume=8 |pages=3183–3190 |issue=12}}</ref>

These two properties—weak interactions and thermodynamic stability—can be recalled to rationalise another property often found in self-assembled systems: the ''sensitivity to perturbations'' exerted by the external environment. These are small fluctuations that alter thermodynamic variables that might lead to marked changes in the structure and even compromise it, either during or after self-assembly. The weak nature of interactions is responsible for the flexibility of the architecture and allows for rearrangements of the structure in the direction determined by thermodynamics. If fluctuations bring the thermodynamic variables back to the starting condition, the structure is likely to go back to its initial configuration. This leads us to identify one more property of self-assembly, which is generally not observed in materials synthesized by other techniques: ''reversibility''.

Self-assembly is a process which is easily influenced by external parameters. This feature can make synthesis rather complex because of the need to control many free parameters. Yet self-assembly has the advantage that a large variety of shapes and functions on many length scales can be obtained.<ref name=for>{{cite journal | vauthors = Lehn JM | title = Toward self-organization and complex matter | journal = Science | volume = 295 | issue = 5564 | pages = 2400–3 | date = March 2002 | pmid = 11923524 | doi = 10.1126/science.1071063 | url = http://dialnet.unirioja.es/servlet/oaiart?codigo=1051047 | s2cid = 37836839 | bibcode = 2002Sci...295.2400L }}</ref>

The fundamental condition needed for nanoscale building blocks to self-assemble into an ordered structure is the simultaneous presence of long-range repulsive and short-range attractive forces.<ref>{{cite journal | vauthors = Forster PM, Cheetham AK |doi=10.1002/1521-3773(20020201)41:3<457::AID-ANIE457>3.0.CO;2-W|title=Open-Framework Nickel Succinate, [Ni<sub>7</sub>(C<sub>4</sub>H<sub>4</sub>O<sub>4</sub>)<sub>6</sub>(OH)<sub>2</sub>(H<sub>2</sub>O)<sub>2</sub>]⋅2H<sub>2</sub>O: A New Hybrid Material with Three-Dimensional Ni−O−Ni Connectivity|year=2002 |journal=Angewandte Chemie International Edition|volume=41|pages=457–459|issue=3|pmid=12491377 }}</ref>

By choosing [[precursor (chemistry)|precursors]] with suitable physicochemical properties, it is possible to exert a fine control on the formation processes that produce complex structures. Clearly, the most important tool when it comes to designing a synthesis strategy for a material, is the knowledge of the chemistry of the building units. For example, it was demonstrated that it was possible to use [[block copolymer|diblock copolymers]] with different block reactivities in order to selectively embed [[maghemite]] nanoparticles and generate periodic materials with potential use as [[waveguides]].<ref>{{cite journal| vauthors = Gazit O, Khalfin R, Cohen Y, Tannenbaum R |title=Self-Assembled Diblock Copolymer "Nanoreactors" as "Catalysts" for Metal Nanoparticle Synthesis|journal=The Journal of Physical Chemistry C|volume=113|issue=2|year=2009|pages=576–583|doi=10.1021/jp807668h}}</ref>

In 2008 it was proposed that every self-assembly process presents a co-assembly, which makes the former term a misnomer. This thesis is built on the concept of mutual ordering of the self-assembling system and its environment.<ref>{{cite journal | vauthors = Uskoković V | title = Isn't self-assembly a misnomer? Multi-disciplinary arguments in favor of co-assembly | journal = Advances in Colloid and Interface Science | volume = 141 | issue = 1–2 | pages = 37–47 | date = September 2008 | pmid = 18406396 | doi = 10.1016/j.cis.2008.02.004 }}</ref>