View source for Poly(N-isopropylacrylamide)

{{Use mdy dates|date=December 2023}}
{{Chembox
| ImageFile = PNIPA.png
| ImageSize = 100px
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| Name = Poly(''N''-isopropylacrylamide)
| IUPACName =
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|Section1={{Chembox Identifiers
| CASNo = 25189-55-3
| PubChem = 16637
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|Section2={{Chembox Properties
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| Formula = (C{{sub|6}}H{{sub|11}}NO){{sub|n}}
| MolarMass = variable
| Appearance = white solid
| Density = 1.1 g/cm<sup>3</sup>
| MeltingPtC = 96
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|Section3={{Chembox Hazards
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'''Poly(''N''-isopropylacrylamide)''' (variously abbreviated '''PNIPA''', '''PNIPAM''', '''PNIPAAm''', '''NIPA''', '''PNIPAA''' or '''PNIPAm''') is a [[temperature-responsive polymer]] that was first [[Polymer synthesis|synthesized]] in the 1950s.<ref name="Schildinfo">{{Cite journal |doi = 10.1016/0079-6700(92)90023-R|title = Poly(N-isopropylacrylamide): Experiment, theory and application|journal = Progress in Polymer Science|volume = 17|issue = 2|pages = 163–249|year = 1992|last1 = Schild|first1 = H.G.}}</ref>   It can be synthesized from ''N''-isopropylacrylamide which is commercially available.  It is synthesized via [[free-radical polymerization]] and is readily functionalized making it useful in a variety of applications.

PNIPA dissolves in water, however, when these solutions are heated in above their [[cloud point]] temperature, they undergo a reversible [[lower critical solution temperature]] (LCST) [[phase transition]] from a soluble hydrated state to an insoluble dehydrated state. Although it is widely believed that this phase transition occurs at {{convert|32|Celsius}},<ref name="Halperin">{{cite journal| author=Halperin A, Kröger M, Winnik FM| title=Poly(N-isopropylacrylamide) Phase Diagrams: Fifty Years of Research. | journal=Angew Chem Int Ed Engl | year= 2015 | volume= 54 | issue= 51 | pages= 15342–67 | pmid=26612195 | doi=10.1002/anie.201506663 }}</ref> the actual temperatures may differ 5 to 10&nbsp;°C (or even more) depending on the polymer concentration,<ref name="Halperin" /> [[molar mass]] of polymer chains, polymer [[dispersity]] as well as terminal moieties.<ref name="Halperin" /><ref name="Aseyev">{{cite book | last1=Aseyev | first1=Vladimir | last2=Tenhu | first2=Heikki | last3=Winnik | first3=Françoise M. | title=Advances in Polymer Science | chapter=Non-ionic Thermoresponsive Polymers in Water | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | year=2010 | volume=242 | issn=0065-3195 | doi=10.1007/12_2010_57 | pages=29–89| isbn=978-3-642-22296-2 }}</ref> Furthermore, other molecules in the polymer solution, such as salts or proteins, can alter the cloud point temperature.<ref name="Kolouchová 2021">{{cite journal | last1=Kolouchová | first1=Kristýna | last2=Lobaz | first2=Volodymyr | last3=Beneš | first3=Hynek | last4=de la Rosa | first4=Victor R. | last5=Babuka | first5=David | last6=Švec | first6=Pavel | last7=Černoch | first7=Peter | last8=Hrubý | first8=Martin | last9=Hoogenboom | first9=Richard | last10=Štěpánek | first10=Petr | last11=Groborz | first11=Ondřej |display-authors=3 | title=Thermoresponsive properties of polyacrylamides in physiological solutions | journal=Polymer Chemistry | publisher=Royal Society of Chemistry (RSC) | year=2021 | volume=12 | issue=35 | pages=5077–5084 | issn=1759-9954 | doi=10.1039/d1py00843a | doi-access=free | hdl=1854/LU-8724379 | s2cid=238937814 | hdl-access=free }}</ref><ref name="Zhang Furyk Sagle Cho 2007 pp. 8916–8924">{{cite journal | last1=Zhang | first1=Yanjie | last2=Furyk | first2=Steven | last3=Sagle | first3=Laura B. | last4=Cho | first4=Younhee | last5=Bergbreiter | first5=David E. | last6=Cremer | first6=Paul S.|display-authors=3  | title=Effects of Hofmeister Anions on the LCST of PNIPAM as a Function of Molecular Weight† | journal=The Journal of Physical Chemistry C | publisher=American Chemical Society (ACS) | volume=111 | issue=25 | year=2007 | issn=1932-7447 |  pmc=2553222 | doi=10.1021/jp0690603 | pages=8916–8924| pmid=18820735 }}</ref>

Since PNIPA expels its liquid contents at a temperature near [[Human body temperature|that of the human body]], PNIPA copolymers have been investigated by many researchers for possible applications in [[tissue engineering]]<ref name="RPE and PNIPAAm">{{cite journal|last=von Recum|first=H. A.|author2=Kikuchi, A.|author3=Okuhara, M.|author4=Sakurai, Y.|author5=Okano, T.|author6=Kim, S. W.|title=Retinal pigmented epithelium cultures on thermally responsive polymer porous substrates|journal= Journal of Biomaterials Science, Polymer Edition|year=1998|volume=9|issue=11|pages=1241–1253|doi=10.1163/156856298X00758|pmid=9860183}}</ref><ref name="CM and PNIPAAm">{{cite journal|last=Lee|first=EL.|author2=von Recum, HA|title=Cell culture platform with mechanical conditioning and nondamaging cellular detachment|journal=J Biomed Mater Res A|year=2010|volume=93|issue=2|pages=411–8|pmid=20358641|doi=10.1002/jbm.a.32754|s2cid=23022529}}</ref> and controlled [[drug delivery]].<ref>{{cite journal | last1 = Chung | first1 = J. E. | last2 = Yokoyama | first2 = M. | last3 = Yamato | first3 = M. | last4 = Aoyagi | first4 = T. | last5 = Sakurai | first5 = Y. | last6 = Okano | first6 = T. |display-authors=3 | year = 1999 | title = Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate) | journal = Journal of Controlled Release | volume = 62 | issue = 1–2| pages = 115–127 | doi=10.1016/S0168-3659(99)00029-2| pmid = 10518643 }}</ref><ref>{{Cite journal |doi = 10.1016/j.colsurfb.2005.10.007|pmid = 16300934|title = Potential application of poly(N-isopropylacrylamide) gel containing polymeric micelles to drug delivery systems|journal = Colloids and Surfaces B: Biointerfaces|volume = 46|issue = 3|pages = 142–146|year = 2005|last1 = Yan|first1 = Hu|last2 = Tsujii|first2 = Kaoru|hdl = 2115/1381| s2cid=31084515 |hdl-access = free}}</ref><ref>{{Cite journal |doi = 10.3933/ApplRheol-19-42064|year = 2009|title = Rheological characterization of the thermal gelation of poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide)co-Acrylic Acid|author=Filipe E. Antunes |author2=Luigi Gentile |author3=Lorena Tavano |author4=Cesare Oliviero Rossi |journal=Applied Rheology }}</ref><ref>{{Cite web |last=Dang |first=Steven |last2=Brady |first2=John |last3=Rel |first3=Ryle |last4=Surineni |first4=Sreenidhi |last5=O'Shaughnessy |first5=Conor |last6=McGorty |first6=Ryan |date=2021-08-02 |title=Core-shell droplets and microcapsules formed through liquid-liquid phase separation of a colloid-polymer mixture |url=https://arxiv.org/abs/2108.01191v1 |access-date=2024-03-17 |website=arXiv.org |language=en}}</ref>

== History ==
The synthesis of poly(''N''-isopropylacrylamide) began with the synthesis of the [[acrylamide]] [[monomers|monomer]] by Sprecht in 1956.<ref>{{ cite patent| country =US | number =2773063 }}</ref>  In 1957, Shearer patented the first application for what would be later identified as PNIPA for the use as a rodent repellent.<ref>{{ cite patent| country =US | number =2790744}}</ref>   Early work was piqued by theoretical curiosity of the material properties of PNIPA.  The first report of PNIPA came in 1968, which elucidated the unique thermal behavior in aqueous solutions.<ref>{{cite journal|title=Solution Properties of Poly(N-isopropylacrylamide) |year=1968 |author1=M. Heskins  |author2=J. E. Guillet |journal=Journal of Macromolecular Science, Part A |volume=2 |issue=8 |pages=1441–1455 |doi=10.1080/10601326808051910}}</ref> The 1980s marked an explosion in interest in PNIPAs with the realization of  potential applications due to its unique thermal behavior in aqueous solutions.<ref name="Schildinfo" />

== Chemical and Physical Properties ==
PNIPA is one of the most studied thermosensitive [[Hydrogel|hydrogel.]]  In dilute solution, it undergoes a [[Coil-globule transition|coil-to-globule transition]].<ref>{{cite journal|last1=Wu|first1=C|last2=Wang |first2=X|title=Globule-to-Coil Transition of a Single Homopolymer Chain in Solution|journal=Physical Review Letters|year=1998|volume=80|issue=18|pages=4092–4094|url=http://ludfc39.u-strasbg.fr/pdflib/polymers/collapse/1998_wu_wang.pdf|doi=10.1103/PhysRevLett.80.4092|access-date=25 September 2010|bibcode=1998PhRvL..80.4092W|archive-url=https://web.archive.org/web/20110721022738/http://ludfc39.u-strasbg.fr/pdflib/polymers/collapse/1998_wu_wang.pdf|archive-date=21 July 2011}}</ref>  PNIPA possesses an inverse solubility upon heating. It changes [[hydrophile|hydrophilicity]] and [[hydrophobe|hydrophobicity]]  abruptly at its [[lower critical solution temperature|LCST]].<ref>{{cite book |last=Somasundaran |first=Ponisseril |year=2004 |title=Encyclopedia of Surface and Colloid Science  |url=https://books.google.com/books?id=epWt0y6OnwcC&q=Encyclopedia+of+Surface+and+Colloid+Science,+2004+Update+Supplement,+Volume+5&pg=PA282 |publisher=Taylor & Francis |isbn=978-0-8247-2154-1 |access-date=2014-02-13 }}</ref>  At lower temperatures PNIPA orders itself in solution in order to [[hydrogen bond]] with the already arranged water molecules.  The water molecules must reorient around the nonpolar regions of PNIPA which results in a decreased [[entropy of mixing|entropy]].  At lower temperatures, such as room temperature, the negative [[enthalpy]] term (<math>\Delta H </math>) from [[hydrogen bond]]ing effects dominates the [[Gibbs free energy]],
<math display="block">\Delta G = \Delta H - T \Delta S \,</math>
causing the PNIPA to absorb water and dissolve in solution.  At higher temperatures, the [[entropy]] term (<math>\Delta S </math>) dominates, causing the PNIPA to release water and phase separate which can be seen in the following demonstration.

{{Gallery
| title = Pictorial Depiction of the LCST Effect of PNIPA
| width = 160
| height = 180
| align = center
| File:PNIPA LCST Before.jpg|alt1=Aqueous solution of PNIPA before heating. The negative enthalpy of hydrogen bonding dominates and PNIPA is dissolved in the solution.|Aqueous solution of PNIPA before heating. The negative enthalpy of hydrogen bonding dominates and PNIPA is dissolved in the solution.
| File:PNIPA LCST After.jpg|alt2=The mixture after heating with a heat gun. The negative entropy of mixing dominates due to the increase in temperature and PNIPA phase separates from the water.|The mixture after heating with a heat gun. The negative entropy of mixing dominates due to the increase in temperature and PNIPA phase separates from the water.
}}

[[File:PNIPA LCST.webm|center|thumb | 200px | A demonstration of the heating of PNIPA to demonstrate the LCST effect.]]

== Synthesis of Heat and pH Sensitive PNIPA ==

'''Homopolymerization'''<ref name="sigaldinfo">{{cite web|url=http://www.sigmaaldrich.com/materials-science/polymer-science/nipam-polymers.html |title=Designing temperature and pH sensitive NIPAM based polymers |publisher=sigmaadlrich.com |access-date=2014-01-25}}</ref>
:The process of free [[radical polymerization]] of a single type of [[monomer]], in this case, ''N''-isopropylacrylamide, to form the polymer is known as a homopolymerization. The radical initiator [[azobisisobutyronitrile]] (AIBN) is commonly used in radical polymerizations.
:[[File:Homopolymerization of PNIPA.png|300px|Homopolymerization of PNIPA]]

'''Copolymerization'''
:A free-radical polymerization of two different [[monomers|monomer]] results in a [[copolymer]]ization. An advantage to a copolymerization includes fine tuning of the [[lower critical solution temperature|LCST]].
:[[File:Copolymerization Synthesis of PNIPA.png|450px|Copolymerization Synthesis of PNIPA]]

'''Terpolymerization'''
:A free-radical polymerization of three different [[monomers|monomer]] is known as a [[copolymer|terpolymerization]]. Advantages to a terpolymerization may include enhancing multiple properties of the polymer including thermosensitivity, pH sensitivity or fine tuning of the [[lower critical solution temperature|LCST]].
:[[File:Terpolymerization Synthesis of PNIPA.png|750px|Terpolymerization Synthesis of PNIPA]]

'''Cross-linked Hydrogel'''
:The reaction scheme below is a [[copolymer|terpolymerization]] to form a [[cross-link]]ed [[gel|hydrogel]]. The reactant [[ammonium persulfate]] (APS) is used in [[polymer chemistry]] as a strong [[oxidizing agent]] that is often used along with [[TMEDA|tetramethylethylenediamine]] (TMEDA) to catalyze the polymerization when making [[polyacrylamide gel electrophoresis|polyacrylamide gels]].
:[[File:Crosslinked Hydrogel Polymerization of PNIPA.png|650px|Crosslinked Hydrogel Polymerization of PNIPA]]

== Synthesis of Chain-End Functionalized PNIPA ==

PNIPA can be functionalized using [[chain transfer]] agents using a free [[radical polymerization]]. The three schemes below demonstrate functionalization using [[chain transfer]] agents (CTA), where one end of the polymer is the [[radical initiator]] and the other is a functionalized group. Functionalization of the polymer chain-end allows for the polymer to be used in many diverse settings and applications. Advantages to a functionalizing the chain-end may include enhancing multiple properties of the polymer including thermosensitivity, pH sensitivity or fine tuning of the [[lower critical solution temperature|LCST]].<ref name="sigaldinfo" />

(1) [[File:Functionalization CTA Scheme 1 of PNIPA.png|450px|Functionalization CTA Scheme 1 of PNIPA]]

(2) [[File:Functionalization CTA Scheme 2 of PNIPA png.png|450px|Functionalization CTA Scheme 2 of PNIPA]]

(3) [[File:Functionalization CTA Scheme 3 of PNIPA png.png|700px|Functionalization CTA Scheme 3 of PNIPA]]

== Applications ==

The versatility of PNIPA has led to finding uses in macroscopic [[gel]]s, [[gel|microgels]],<ref>{{Cite journal |last1=Widmann |first1=Tobias |last2=Kreuzer |first2=Lucas P. |last3=Hohn |first3=Nuri |last4=Bießmann |first4=Lorenz |last5=Wang |first5=Kun |last6=Rinner |first6=Stephan |last7=Moulin |first7=Jean-François |last8=Schmid |first8=Andreas J. |last9=Hannappel |first9=Yvonne |last10=Wrede |first10=Oliver |last11=Kühnhammer |first11=Matthias |display-authors=3 |date=2019-12-10 |title=Hydration and Solvent Exchange Induced Swelling and Deswelling of Homogeneous Poly(N-isopropylacrylamide) Microgel Thin Films |journal=Langmuir |volume=35 |issue=49 |pages=16341–16352 |doi=10.1021/acs.langmuir.9b03104 |pmid=31714092 |s2cid=207940427 |issn=0743-7463}}</ref> membranes, [[sensor]]s, [[biosensor]]s, [[thin film]]s,<ref>{{Cite journal |last1=Kreuzer |first1=Lucas P. |last2=Widmann |first2=Tobias |last3=Hohn |first3=Nuri |last4=Wang |first4=Kun |last5=Bießmann |first5=Lorenz |last6=Peis |first6=Leander |last7=Moulin |first7=Jean-Francois |last8=Hildebrand |first8=Viet |last9=Laschewsky |first9=André |last10=Papadakis |first10=Christine M. |last11=Müller-Buschbaum |first11=Peter|display-authors=3 |date=2019-05-14 |title=Swelling and Exchange Behavior of Poly(sulfobetaine)-Based Block Copolymer Thin Films |journal=Macromolecules |volume=52 |issue=9 |pages=3486–3498 |doi=10.1021/acs.macromol.9b00443 |bibcode=2019MaMol..52.3486K |s2cid=155174181 |issn=0024-9297}}</ref><ref>{{Cite journal |last1=Kreuzer |first1=Lucas P. |last2=Widmann |first2=Tobias |last3=Bießmann |first3=Lorenz |last4=Hohn |first4=Nuri |last5=Pantle |first5=Johannes |last6=Märkl |first6=Raphael |last7=Moulin |first7=Jean-François |last8=Hildebrand |first8=Viet |last9=Laschewsky |first9=André |last10=Papadakis |first10=Christine M. |last11=Müller-Buschbaum |first11=Peter|display-authors=3 |date=2020-04-28 |title=Phase Transition Kinetics of Doubly Thermoresponsive Poly(sulfobetaine)-Based Diblock Copolymer Thin Films |journal=Macromolecules |volume=53 |issue=8 |pages=2841–2855 |doi=10.1021/acs.macromol.0c00046 |bibcode=2020MaMol..53.2841K |s2cid=216346530 |issn=0024-9297}}</ref><ref>{{Cite journal |last1=Kreuzer |first1=Lucas P. |last2=Widmann |first2=Tobias |last3=Aldosari |first3=Nawarah |last4=Bießmann |first4=Lorenz |last5=Mangiapia |first5=Gaetano |last6=Hildebrand |first6=Viet |last7=Laschewsky |first7=André |last8=Papadakis |first8=Christine M. |last9=Müller-Buschbaum |first9=Peter|display-authors=3 |date=2020-10-27 |title=Cyclic Water Storage Behavior of Doubly Thermoresponsive Poly(sulfobetaine)-Based Diblock Copolymer Thin Films |journal=Macromolecules |volume=53 |issue=20 |pages=9108–9121 |doi=10.1021/acs.macromol.0c01335 |bibcode=2020MaMol..53.9108K |s2cid=226323489 |issn=0024-9297}}</ref> [[tissue engineering]], and [[drug delivery]].   The tendency of aqueous solutions of PNIPA to increase in [[viscosity]] in the presence of [[hydrophobe|hydrophobic molecules]] has made it excellent for [[enhanced oil recovery|tertiary oil recovery]].

As aqueous solutions of PNIPA have their [[lower critical solution temperature]] in temperatures around [[human body temperature]]s, these polymers can be dissolved in water at room temperature and administered into body.<ref name="Groborz 2022"/> However, upon the administration, these polymers phase-separate and form insoluble aggregates at site of administration (this process is called [[thermogelling]]).<ref name="Groborz 2022"/> When PNIPA is administered into muscles of mice, its half-life was approximately 48 days (''M''<sub>w</sub> = 20&nbsp;kg/mol) and 66 days (''M''<sub>w</sub> = 32&nbsp;kg/mol) and caused no local or systemic pathologies.<ref name="Groborz 2022">{{cite journal | last=Groborz | first=Ondřej | last2=Kolouchová | first2=Kristýna | last3=Pankrác | first3=Jan | last4=Keša | first4=Peter | last5=Kadlec | first5=Jan | last6=Krunclová | first6=Tereza | last7=Pierzynová | first7=Aneta | last8=Šrámek | first8=Jaromír | last9=Hovořáková | first9=Mária | last10=Dalecká | first10=Linda | last11=Pavlíková | first11=Zuzana | last12=Matouš | first12=Petr | last13=Páral | first13=Petr | last14=Loukotová | first14=Lenka | last15=Švec | first15=Pavel | last16=Beneš | first16=Hynek | last17=Štěpánek | first17=Lubomír | last18=Dunlop | first18=David | last19=Melo | first19=Carlos V. | last20=Šefc | first20=Luděk | last21=Slanina | first21=Tomáš | last22=Beneš | first22=Jiří | last23=Van Vlierberghe | first23=Sandra | last24=Hoogenboom | first24=Richard | last25=Hrubý | first25=Martin |display-authors=3| title=Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers | journal=Advanced Healthcare Materials | volume=11 | issue=22 | date=2022 | pmid = 36153823 | issn=2192-2640 | doi=10.1002/adhm.202201344 | doi-access=free | page=| hdl=1854/LU-01GVZJXMSK2RW8QTJ41MBSHE1C | hdl-access=free }}</ref> Such phase separated hydrogels can be used for local  [[drug delivery]] applications.<ref>{{cite journal|title=Thermally on-off switching polymers for drug permeation and release |year=1990 |author1=A. T. Okano |author2=Y. H. Bae |author3=H. Jacobs |author4=S. W. Kim |journal=Journal of Controlled Release|volume=11 |issue=1–3 |pages= 255–265 |doi=10.1016/0168-3659(90)90138-j}}</ref>  The PNIPA can be placed in a solution of bioactive molecules,  which allows the bioactive molecules to penetrate the PNIPA.  The PNIPA can then be placed [[in vivo]], where there is a rapid release of [[biomolecule]]s due to the initial gel collapse and an ejection of the biomolecules into the surrounding media, followed by a slow release of biomolecules due to surface pore closure.<ref>{{cite journal|title=Thermally reversible hydrogels: II. Delivery and selective removal of substances from aqueous solutions|year=1986 |author1=Allan S. Hoffman |author2=Ali Afrassiabi |author3=Liang Chang Dong |journal=Journal of Controlled Release|volume=4 |issue=3 |pages= 213–222 |doi=10.1016/0168-3659(86)90005-2}}</ref>

PNIPA have also been used in [[pH-sensitive polymers|pH-sensitive]] [[drug delivery]] systems. Some examples of these drug delivery systems may include the intestinal delivery of human calcitonin,<ref name="examples">{{cite journal|last=Schmaljohann|first=Dirk|title=Thermo- and pH-responsive polymers in drug delivery|journal=Advanced Drug Delivery Reviews|year=2006|volume=58|issue=15|pages=1655–70|url=http://web.ics.purdue.edu/~jfleary/nanomedicine_course_2011/Lecture_6/Lecture%206%20References/Schmaljohann%202006.pdf|publisher=Elsevier|doi=10.1016/j.addr.2006.09.020|pmid=17125884|access-date=13 March 2014}}</ref> delivery of insulin,<ref name="examples" /> and the delivery of ibuprofen.<ref>{{cite journal|last=Zhu|first=Senmin|author2=Zhou, Zhengyang |author3=Zhang, Di |title=Grafting of thermo-responsive polymer inside mesoporous silica with large pore size using ATRP and investigation of its use in drug release|journal=J. Mater. Chem.|date=15 March 2007|volume=17|issue=23|pages=2428–2433|doi=10.1039/b618834f}}</ref>  When radiolabeled PNIPA copolymers with different molecular weights were intravenously injected to rats, it was found that the glomerular filtration threshold of the polymer was around 32 000&nbsp;g/mol.<ref>{{cite journal | last1 = Bertrand | first1 = N. | last2 = Fleischer | first2 = J.G. | last3 = Wasan | first3 = K.M. | last4 = Leroux | first4 = J.C.|display-authors=3 | year = 2009 | title = Pharmacokinetics and biodistribution of N-isopropylacrylamide copolymers for the design of pH-sensitive liposomes | journal = Biomaterials | volume = 30 | issue = 13| pages = 2598–2605 | doi=10.1016/j.biomaterials.2008.12.082| pmid = 19176241 }}</ref>

PNIPA have been used in [[electroactive polymers|gel actuators]], which convert external stimuli into mechanical motion.<ref>{{cite journal | last1=Chandorkar | first1=Yashoda | last2=Castro Nava | first2=Arturo | last3=Schweizerhof | first3=Sjören | last4=Van Dongen | first4=Marcel | last5=Haraszti | first5=Tamás | last6=Köhler | first6=Jens | last7=Zhang | first7=Hang | last8=Windoffer | first8=Reinhard | last9=Mourran | first9=Ahmed | last10=Möller | first10=Martin | last11=De Laporte | first11=Laura |display-authors=3| title=Cellular responses to beating hydrogels to investigate mechanotransduction | journal=Nature Communications | publisher=Springer Science and Business Media LLC | volume=10 | issue=1 | date=2019-09-06 | page=4027 | issn=2041-1723 | doi=10.1038/s41467-019-11475-4| pmid=31492837 | pmc=6731269 | bibcode=2019NatCo..10.4027C }}</ref> Upon heating above the [[lower critical solution temperature|LCST]], the [[gel|hydrogel]] goes from [[hydrophile|hydrophilic]] to [[hydrophobe|hydrophobic]] state.<ref>{{cite journal|author1=Xiaobo Zhang|author2=Cary L. Pint|author3=Min Hyung Lee|author4=Bryan Edward Schubert|author5=Arash Jamshidi|author6=Kuniharu Takei|author7=Hyunhyub Ko|author8=Andrew Gillies|last9=Bardhan|first9=Rizia|author-link9=Rizia Bardhan|author10=Jeffrey J. Urban|author11=Ming Wu|display-authors=3|year=2011|title=Optically- and Thermally-Responsive Programmable Materials Based on Carbon Nanotube-Hydrogel Polymer Composites|journal=Nano Letters|volume=11|issue=8|pages=3239–3244|bibcode=2011NanoL..11.3239Z|doi=10.1021/nl201503e|pmid=21736337|s2cid=14317595|author13=Ali Javey|author12=Ronald Fearing}}</ref>  This conversion results in an expulsion of water which causes a physical [[conformational change]], creating a mechanical hinge movement.

Furthermore, PNIPA-based thin films can be applied as nano-switches featuring multiple distinct thin-film states, which is based on the [[cononsolvency]] effect.<ref>{{Cite journal |last1=Kreuzer |first1=Lucas P. |last2=Geiger |first2=Christina |last3=Widmann |first3=Tobias |last4=Wang |first4=Peixi |last5=Cubitt |first5=Robert |last6=Hildebrand |first6=Viet |last7=Laschewsky |first7=André |last8=Papadakis |first8=Christine M. |last9=Müller-Buschbaum |first9=Peter|display-authors=3 |date=2021-08-10 |title=Solvation Behavior of Poly(sulfobetaine)-Based Diblock Copolymer Thin Films in Mixed Water/Methanol Vapors |journal=Macromolecules |volume=54 |issue=15 |pages=7147–7159 |doi=10.1021/acs.macromol.1c01179 |bibcode=2021MaMol..54.7147K |s2cid=237724968 |issn=0024-9297}}</ref><ref>{{Cite journal |last1=Kreuzer |first1=Lucas P. |last2=Lindenmeir |first2=Christoph |last3=Geiger |first3=Christina |last4=Widmann |first4=Tobias |last5=Hildebrand |first5=Viet |last6=Laschewsky |first6=André |last7=Papadakis |first7=Christine M. |last8=Müller-Buschbaum |first8=Peter|display-authors=3 |date=2021-02-09 |title=Poly(sulfobetaine) versus Poly(N-isopropylmethacrylamide): Co-Nonsolvency-Type Behavior of Thin Films in a Water/Methanol Atmosphere |journal=Macromolecules |volume=54 |issue=3 |pages=1548–1556 |doi=10.1021/acs.macromol.0c02281 |bibcode=2021MaMol..54.1548K |s2cid=234184714 |issn=0024-9297}}</ref><ref>{{Cite journal |last1=Geiger |first1=Christina |last2=Reitenbach |first2=Julija |last3=Henschel |first3=Cristiane |last4=Kreuzer |first4=Lucas P. |last5=Widmann |first5=Tobias |last6=Wang |first6=Peixi |last7=Mangiapia |first7=Gaetano |last8=Moulin |first8=Jean-François |last9=Papadakis |first9=Christine M. |last10=Laschewsky |first10=André |last11=Müller-Buschbaum |first11=Peter|display-authors=3 |date=November 2021 |title=Ternary Nanoswitches Realized with Multiresponsive PMMA‐ b ‐PNIPMAM Films in Mixed Water/Acetone Vapor Atmospheres |url=https://onlinelibrary.wiley.com/doi/10.1002/adem.202100191 |journal=Advanced Engineering Materials |language=en |volume=23 |issue=11 |page=2100191 |doi=10.1002/adem.202100191 |s2cid=235560292 |issn=1438-1656|doi-access=free }}</ref>

== References ==
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[[Category:Polyamides]]
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[[Category:Acrylamides]]