Mechano-regulatory cellular behaviors of NIH/3T3 in response to the storage modulus of liquid crystalline substrates

Chen, Yang; Wang, Lei; Huang, Hao; Tan, Ruizhe; Zhao, Jupeng; Yang, Shenyu; Zeng, Rong; Wu, Hao; Zhang, Jiaqing; Yu, Bin; Tu, Mei

doi:10.1016/j.jmbbm.2015.11.005

Cited by 9 publications

(4 citation statements)

References 45 publications

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“…As a biopolymer, extracellular matrix shows a power-law mechanical response similar to cells. 34 However, most conventional biomaterials (as mentioned above) are unable to recapitulate the mechanical microenvironment of biological system. On the one hand, the stiffness of plastic dishes currently used as cell culture plates is several orders of magnitude higher than that of in vivo extracellular microenvironment sensed by cells, 35 on the other hand, most of polymers/composites served as cell matrices tended to deform abruptly under shear stresses and formed large deformations due to the nonlinear viscoelastic behavior at low shear rates.…”

Section: Discussionmentioning

confidence: 99%

Liquid crystalline matrix-induced viscoelastic mechanical stimulation modulates activation and phenotypes of macrophage

et al. 2023

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Accumulating evidence indicates that the mechanical microenvironment exerts profound influences on inflammation and immune modulation, which are likely to be key factors in successful tissue regeneration. The elastic modulus (Em) of the matrix may be a useful adjustable property to control macrophage activation and the overall inflammatory response. This study constituted a series of Em-tunable liquid crystalline cell model (HpCEs) resembling the viscoelastic characteristic of ECM and explored how mechanical microenvironment induced by liquid crystalline soft matter matrix affected macrophage activation and phenotypes. We have shown that HpCEs prepared in this work exhibited typical cholesteric liquid crystal phase and distinct viscoelastic rheological characteristics. All liquid crystalline HpCE matrices facilitated macrophages growth and maintained cell activity. Macrophages in lower-Em HpCE matrices were more likely to polarize toward the pro-inflammatory M1 phenotype. Conversely, the higher-Em HpCEs induced macrophages into an elongated shape and upregulated M2-related markers. Furthermore, the higher-Em HpCEs (HpCE-O1, HpCE-H2, HpCE-H1) could coax sequential polarization states of RAW264.7 from a classically activated “M1” state toward alternatively activated “M2” state in middle and later stage of cell culture (within 3–7 days in this work), suggesting that the HpCE-based strategies could manipulate the local immune microenvironment and promote the dominance of the pro-inflammatory signals in early stages, while M2 macrophages in later stages. The liquid crystalline soft mode fabricated in this work maybe offer a new design guideline for in vitro cell models and applications.

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Section: Discussionmentioning

confidence: 99%

Liquid crystalline matrix-induced viscoelastic mechanical stimulation modulates activation and phenotypes of macrophage

et al. 2023

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“…Liquid crystalline materials are therefore believed potentially useful for engineering interfaces for living cells 35 . Our previous study showed that small changes in the elastic modulus of OPC substrate could produce intense cell responses that influenced cell fate and functions, 14,36 which mainly resulted from cell sensitive response to the mechanical stimuli of liquid crystalline matrix due to both elastic and viscous elements combined in these liquid crystalline materials 37,38 . However, the hydrophobicity of OPC made it lack active sites participating in the first cellular events.…”

Section: Discussionmentioning

confidence: 99%

“…NIH/3 T3 cells were highly sensitive to the elastic modulus of liquid crystalline OPC substrates and small changes in the elastic modulus could give rise to intense cell responses that influenced cell fate and properties. OPC substrates with intermediate elastic modulus (12,312 Pa, 7,228 Pa) provided more favorable conditions for cell proliferation, spreading, cytoskeleton organization and high phosphorylation levels of paxillin and ERK1/2 14 . Following research 15 based on liquid crystal/polyurethane (LC/PU) composite matrix indicated that addition of varying LC concentration had great effects on surface morphology and elastic modulus of LC/PU composite substrates.…”

Section: Introductionmentioning

confidence: 99%

Enhanced cell affinity and osteogenic differentiation of liquid crystal‐based substrate via surface bio‐functionalization

Yang

Huang

Jian

et al. 2020

J Biomedical Materials Res

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Regulation of cell‐substrate interactions is an important factor for modulating cell behaviors. Tailoring the physical and chemical properties of the substrates to better mimic the extracellular matrix (ECM) of native tissue is a more effective strategy for enhancing the cell‐substrate contact. In current work, we aim at improving surface bioactivity based on the liquid crystalline substrates for the enhancement in cell affinity and osteogenic differentiation. Polydopamine (PDOPA) adhesive coating was used as a reactive platform for the immobilization of chitooligosaccharide (COS) on the octyl hydroxypropyl cellulose ester (OPC) substrate to generate active OPC‐PDOPA‐COSs liquid crystalline substrates. Results demonstrated that PDOPA‐coated OPC surfaces showed remarkably improved hydrophility and increased elastic modulus, leading to better initial cell attachment. Subsequent COS immobilization on the OPC‐PDOPA layer could induce promotion of cell proliferation, polarization and cytoskeleton formation. Rat bone marrow mesenchymal stem cells (rBMSCs) seeded on the OPC‐PDOPA‐COSs showed higher alkaline phosphatase (ALP) activity, calcium deposition, and up‐regulated bone‐related genes expression, including BMP‐2, RUNx‐2, COL‐I and OCN. In conclusion, surface biofunctionalization on the OPC‐based liquid crystalline substrates could come into being the appropriate combination of surface chemistry and liquid crystalline characteristic that simulating in vivo ECM environment, resulting in a favorable support to enhance positive cell‐substrate interactions.

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“…Our previous study had demonstrated that NIH/3T3 cells were highly sensitive to the Em of LC OPC substrates and small changes in the Em could produce intense cell responses that influenced cell fate and properties. 53 Herein, formation of rich-OPC domains, which combine the elastic properties of polymers with the order inherent in LC, 54 gave rise to a soft elastic response that made the LC/PU composite substrates present biologically relevant mechanical properties sequentially modulated hUC-MSCs osteogenic differentiation, and small changes in the Em of LC/PU composite substrates resulted in distinct cell functions. The fact that LC-10/PU and LC-30/PU showed benefit to hUC-MSCs attachment, spreading, proliferation, and osteogenic differentiation might be ascribed to their suitable surface microstructures and more compliant mechanically activities, which provided optimal stiffness and contractility to the cellular mechanical stresses that were essential for mechanotransduction.…”

Section: Discussionmentioning

confidence: 99%

The effects of liquid crystal-based composite substrates on cell functional responses of human umbilical cord-derived mesenchymal stem cells by mechano-regulatory process

Shang

Zhang

et al. 2017

J Biomater Appl

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Physical properties of extracellular matrix, including elasticity and microstructure, have been considered as important factors inducing stem cell differentiation. This study developed a novel type of liquid crystal-based matrix by combining the elastic property of polyurethane with viscoelastic liquid crystal to generate a soft elastic response resembling physical microenvironment of stem cell niche, and explored the mechano-driving cell behaviors. Addition of varying liquid crystal concentration (10 wt%, 30 wt% and 50 wt%) had great effects on surface morphology and elastic modulus of liquid crystal/ polyurethane composite substrates. Changes in microstructure and elastic modulus of the substrates could cause intense cell responses that influenced cell properties, including proliferation, adhesion, and osteogenic differentiation. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) cultured on both liquid crystal-10/polyurethane and liquid crystal-30/polyurethane substrates exhibited higher viability, more actin filament, and larger spreading area while liquid crystal-50/polyurethane substrates seemed not to favor cell attachment and spreading. Alkaline phosphatase activity and calcium deposition were significantly improved with hUC-MSCs on both liquid crystal-10/ polyurethane and liquid crystal-30/ polyurethane substrates, and the maximal alkaline phosphatase activity was observed in liquid crystal-10/ polyurethane while the lowest in liquid crystal-50/ polyurethane. Osteopontin was upregulated to a high level in both liquid crystal-10/ polyurethane and liquid crystal-30/ polyurethane groups after 14 days culturing; the maximal expression of osteocalcin and related transcription factor 2 were found in liquid crystal-10/ polyurethane group on day 21. Our findings revealed that hUC-MSCs could intensely sense the bioactive patterns and soft-matter feature of liquid crystal domains and subsequently modulated cell behaviors, which may prove useful in the development of new class of biomaterials for applications in tissue engineering and regenerative medicine.

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Mechano-regulatory cellular behaviors of NIH/3T3 in response to the storage modulus of liquid crystalline substrates

Cited by 9 publications

References 45 publications

Liquid crystalline matrix-induced viscoelastic mechanical stimulation modulates activation and phenotypes of macrophage

Liquid crystalline matrix-induced viscoelastic mechanical stimulation modulates activation and phenotypes of macrophage

Enhanced cell affinity and osteogenic differentiation of liquid crystal‐based substrate via surface bio‐functionalization

The effects of liquid crystal-based composite substrates on cell functional responses of human umbilical cord-derived mesenchymal stem cells by mechano-regulatory process

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