PMID- 34533951 OWN - NLM STAT- MEDLINE DCOM- 20210930 LR - 20210930 IS - 1520-5827 (Electronic) IS - 0743-7463 (Linking) VI - 37 IP - 38 DP - 2021 Sep 28 TI - Thin Thermoresponsive Polymer Films for Cell Culture: Elucidating an Unexpected Thermal Phase Behavior by Atomic Force Microscopy. PG - 11386-11396 LID - 10.1021/acs.langmuir.1c02003 [doi] AB - Application of poly-N-isopropylacrylamide (PNIPAM) and its more hydrophobic copolymers with N-tert-butylacrylamide (NtBA) as supports for cell sheets has been validated in numerous studies. The binary systems of these polymers with water are characterized by a lower critical solution temperature (LCST) in a physiologically favorable region. Upon lowering the temperature below the LCST, PNIPAM chains undergo a globule-to-coil transition, causing the film dissolution and cell sheet detachment. The character of the PNIPAM-water miscibility behavior is rather complex and not completely understood. Here, we applied atomic force microscopy to track the phase transition in thin films of linear thermoresponsive (co)polymers (PNIPAM and PNIPAM-co-NtBA) prepared by spin-coating. We studied the films' Young's modulus, roughness, and thickness in air and in distilled water in a full thermal cycle. In dry films, in the absence of water, all the measured parameters remained invariant. The swollen films in water above the LCST were softer by 2-3 orders of magnitude and about 10 times rougher than the corresponding dry films. Upon lowering the temperature to the LCST, the films passed through the phase transition observed as a drastic drop of Young's modulus (about an order of magnitude) and decrease in roughness in both polymers in a narrow temperature range. However, the films did not lose their integrity and demonstrated almost fully reversible changes in the mechanical properties and roughness. The thermal dependence of the films' thickness confirmed that they dissolved only partially and required an external force to induce the complete destruction. The reversible thermal behavior which is generally not expected from non-cross-linked polymers is a key finding, especially with respect to their practical application in cell culture. Both the thermodynamic and kinetic factors, as well as the confinement effect, may be responsible for this peculiar film robustness, which requires overcooling and the aid of an external force to destroy the film. FAU - Frolova, Anastasia AU - Frolova A AUID- ORCID: 0000-0003-1073-2611 AD - Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. AD - World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. FAU - Ksendzov, Evgenii AU - Ksendzov E AD - Department of Chemistry, Belarusian State University, 14 Leningradskaya Street, Minsk 220006, Belarus. AD - Research Institute for Physical Chemical Problems of the Belarusian State University, 14 Leningradskaya Street, Minsk 220006, Belarus. FAU - Kostjuk, Sergei AU - Kostjuk S AUID- ORCID: 0000-0002-7466-3662 AD - Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. AD - Department of Chemistry, Belarusian State University, 14 Leningradskaya Street, Minsk 220006, Belarus. AD - Research Institute for Physical Chemical Problems of the Belarusian State University, 14 Leningradskaya Street, Minsk 220006, Belarus. FAU - Efremov, Yuri AU - Efremov Y AD - Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. AD - World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. FAU - Solovieva, Anna AU - Solovieva A AD - N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 4 Kosygin Street, Moscow 119991, Russia. FAU - Rochev, Yuri AU - Rochev Y AD - Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. AD - National University of Ireland Galway, Galway H91 CF50, Ireland. FAU - Timashev, Peter AU - Timashev P AD - Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. AD - World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. AD - N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 4 Kosygin Street, Moscow 119991, Russia. AD - Chemistry Department, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow 119991, Russia. FAU - Kotova, Svetlana AU - Kotova S AD - Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119991, Russia. AD - N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 4 Kosygin Street, Moscow 119991, Russia. LA - eng PT - Journal Article DEP - 20210917 PL - United States TA - Langmuir JT - Langmuir : the ACS journal of surfaces and colloids JID - 9882736 RN - 0 (Polymers) SB - IM MH - *Cell Culture Techniques MH - Microscopy, Atomic Force MH - Phase Transition MH - *Polymers MH - Temperature EDAT- 2021/09/18 06:00 MHDA- 2021/10/01 06:00 CRDT- 2021/09/17 17:13 PHST- 2021/09/18 06:00 [pubmed] PHST- 2021/10/01 06:00 [medline] PHST- 2021/09/17 17:13 [entrez] AID - 10.1021/acs.langmuir.1c02003 [doi] PST - ppublish SO - Langmuir. 2021 Sep 28;37(38):11386-11396. doi: 10.1021/acs.langmuir.1c02003. Epub 2021 Sep 17.