Abstract
Cells are capable of sensing the mechanical microenvironment of tissues and responding accordingly by changing their transcriptional activity and modifying their behavior. To understand the role of mechanical stimulation in regulating stem cell fates, we prepared a novel liquid crystalline hydroxypropyl cellulose ester (CnPC) with viscoelastic features to mimic the mechanical properties of native tissue and guide stem cell behavior. The results revealed that the elastic modulus (G') and viscous modulus (G) of CnPCs were frequency-dependent and their rheological characteristic exhibited linear viscoelastic behavior in the frequency range of 0.1 ~ 100 rad/s. The CnPC soft matrices could induce appropriate cell activity and contraction in rat bone marrow mesenchymal stem cells (rBMSCs) within a relatively low range of elastic modulus (6–13 kPa), which was attributed to their high flexibility and sensitivity to low forces. Therefore, the CnPC was able to sense small cell traction forces, far beyond the capabilities of synthetic polymers and composites. Moreover, the rBMSCs facilitated stiffer matrix (1–13 kPa in this work) during the soft contact process. Although the initial attachment of cells was tension-independent, subsequent processes such as adhesion, proliferation, spreading, and actin cytoskeleton formation significantly depended on mechano-transduction induced by the viscoelasticity of the CnPC. rBMSCs seeded on the CnPC with higher G and G' (C6PC-1, C8PC-2 and C8PC-1) exhibited enhanced cytoskeleton formation, stable nuclear Yeast Aspartyl Protease (YAP) localization and osteogenic differentiation. The soft liquid crystal model developed in this work provides a promising approach for studying the response of stem cell to mechanical stimulation and the consequent effects of mechanical transduction on cell behavior and function.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Ahamed MI, Prasad R (2021) Advanced antimicrobial materials and applications. Gateway East, Singapore. https://doi.org/10.1007/978-981-15-7098-8
Aragona M, Panciera T, Manfrin A et al (2013) A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell 154:1047–1059. https://doi.org/10.1016/j.cell.2013.07.042
Cameron AR, Frith JE, Cooper-White JJ (2011) The influence of substrate creep on mesenchymal stem cell behaviour and phenotype. Biomaterials 32:5979–5993. https://doi.org/10.1016/j.biomaterials.2011.04.003
Chaudhuri O, Cooper-White J, Janmey PA et al (2020) Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584:535–546. https://doi.org/10.1038/s41586-020-2612-2
Chen Y, Wang L, Huang H et al (2016) Mechano-regulatory cellular behaviors of NIH/3T3 in response to the storage modulus of liquid crystalline substrates. J Mech Behav Biomed Mater 57:42–54. https://doi.org/10.1016/j.jmbbm.2015.11.005
Chiang MY, Yangben Y, Lin NJ et al (2013) Relationships among cell morphology, intrinsic cell stiffness and cell–substrate interactions. Biomaterials 34:9754–9762. https://doi.org/10.1016/j.biomaterials.2013.09.014
Chu G, Yuan Z, Zhu C et al (2019) Substrate stiffness- and topography-dependent differentiation of annulus fibrosus-derived stem cells is regulated by Yes-associated protein. Acta Biomater 92:254–264. https://doi.org/10.1016/j.actbio.2019.05.013
Danesin R, Brun P, Roso M et al (2012) Self-assembling peptide-enriched electrospun polycaprolactone scaffolds promote the h-osteoblast adhesion and modulate differentiation-associated gene expression. Bone 51:851–859. https://doi.org/10.1016/j.bone.2012.08.119
Elosegui-Artola A, Oria R, Chen Y et al (2016) Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nat Cell Biol 18:540–548. https://doi.org/10.1038/ncb3336
Fakhry M (2013) Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts. WJSC 5:136. https://doi.org/10.4252/wjsc.v5.i4.136
Fioretta ES, Fledderus JO, Baaijens FPT, Bouten CVC (2012) Influence of substrate stiffness on circulating progenitor cell fate. J Biomech 45:736–744. https://doi.org/10.1016/j.jbiomech.2011.11.013
Flores-Rojas GG, Vázquez E, López-Saucedo F et al (2023) Lignocellulosic membrane grafted with 4-vinylpiridine using radiation chemistry: antimicrobial activity of loaded vancomycin. Cellulose. https://doi.org/10.1007/s10570-023-05089-9
Focher B, Palma MT, Canetti M et al (2001) Structural differences between non-wood plant celluloses: evidence from solid state NMR, vibrational spectroscopy and X-ray diffractometry. Ind Crops Prod 13:193–208. https://doi.org/10.1016/S0926-6690(00)00077-7
Fusco S, Panzetta V, Embrione V, Netti PA (2015) Crosstalk between focal adhesions and material mechanical properties governs cell mechanics and functions. Acta Biomater 23:63–71. https://doi.org/10.1016/j.actbio.2015.05.008
Gattazzo F, Urciuolo A, Bonaldo P (2014) Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim et Biophys Acta (BBA)-Gen Subj 1840:2506–2519. https://doi.org/10.1016/j.bbagen.2014.01.010
Geng Y, Pei X, He X et al (2018) Preparation and Characterization of Esterified Bamboo Flour by an in Situ Solid Phase Method. Polymers 10:920. https://doi.org/10.3390/polym10080920
Goldmann WH (2012) Mechanotransduction in cells1. Cell Biol Int 36:567–570. https://doi.org/10.1042/CBI20120071
Hao J, Zhang Y, Wang Y et al (2014) Role of extracellular matrix and YAP/TAZ in cell fate determination. Cell Signal 26:186–191. https://doi.org/10.1016/j.cellsig.2013.11.006
Hao J, Zhang Y, Jing D et al (2015) Mechanobiology of mesenchymal stem cells: Perspective into mechanical induction of MSC fate. Acta Biomater 20:1–9. https://doi.org/10.1016/j.actbio.2015.04.008
Helfrich W (1973) Elastic Properties of Lipid Bilayers: Theory and Possible Experiments. Zeitschrift Für Naturforschung C 28:693–703. https://doi.org/10.1515/znc-1973-11-1209
Hsieh WT, Liu YS, Lee Y et al (2016) Matrix dimensionality and stiffness cooperatively regulate osteogenesis of mesenchymal stromal cells. Acta Biomater 32:210–222. https://doi.org/10.1016/j.actbio.2016.01.010
Hu JKH, Du W, Shelton SJ et al (2017) An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice. Cell Stem Cell 21:91-106.e6. https://doi.org/10.1016/j.stem.2017.03.023
Huang B, Ge JJ, Li Y, Hou H (2007) Aliphatic acid esters of (2-hydroxypropyl) cellulose—Effect of side chain length on properties of cholesteric liquid crystals. Polymer 48:264–269. https://doi.org/10.1016/j.polymer.2006.11.033
Janoštiak R, Pataki AC, Brábek J, Rösel D (2014) Mechanosensors in integrin signaling: The emerging role of p130Cas. Eur J Cell Biol 93:445–454. https://doi.org/10.1016/j.ejcb.2014.07.002
Jansen KA, Atherton P, Ballestrem C (2017) Mechanotransduction at the cell-matrix interface. Semin Cell Dev Biol 71:75–83. https://doi.org/10.1016/j.semcdb.2017.07.027
Keogh MB, O’Brien FJ, Daly JS (2010) Substrate stiffness and contractile behaviour modulate the functional maturation of osteoblasts on a collagen–GAG scaffold. Acta Biomater 6:4305–4313. https://doi.org/10.1016/j.actbio.2010.06.001
Koo JH, Guan KL (2018) Interplay between YAP/TAZ and Metabolism. Cell Metab 28:196–206. https://doi.org/10.1016/j.cmet.2018.07.010
Lagerwall JPF, Scalia G (2012) A new era for liquid crystal research: Applications of liquid crystals in soft matter nano-, bio- and microtechnology. Curr Appl Phys 12:1387–1412. https://doi.org/10.1016/j.cap.2012.03.019
Lai M, Jin Z, Qiao W (2017) Surface immobilization of gelatin onto TiO2 nanotubes to modulate osteoblast behavior. Colloids Surf, B 159:743–749. https://doi.org/10.1016/j.colsurfb.2017.08.043
Lin KC, Park HW, Guan KL (2018) Deregulation and Therapeutic Potential of the Hippo Pathway in Cancer. Annu Rev Cancer Biol 2:59–79. https://doi.org/10.1146/annurev-cancerbio-030617-050202
López-Velázquez D, Hernández-Sosa AR, Pérez E (2015) Effect of the degree of substitution in the transition temperatures and hydrophobicity of hydroxypropyl cellulose esters. Carbohyd Polym 125:224–231. https://doi.org/10.1016/j.carbpol.2014.12.086
Marozas IA, Anseth KS, Cooper-White JJ (2019) Adaptable boronate ester hydrogels with tunable viscoelastic spectra to probe timescale dependent mechanotransduction. Biomaterials 223:119430. https://doi.org/10.1016/j.biomaterials.2019.119430
Meng Z, Qiu Y, Lin KC et al (2018) RAP2 mediates mechanoresponses of the Hippo pathway. Nature 560:655–660. https://doi.org/10.1038/s41586-018-0444-0
Rey AD (2010) Liquid crystal models of biological materials and processes. Soft Matter 6:3402–3429. https://doi.org/10.1039/B921576J
Scott LE, Mair DB, Narang JD et al (2015) Fibronectin fibrillogenesis facilitates mechano-dependent cell spreading, force generation, and nuclear size in human embryonic fibroblasts. Integr Biol 7:1454–1465. https://doi.org/10.1039/c5ib00217f
Shiu JY, Aires L, Lin Z, Vogel V (2018) Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction. Nat Cell Biol 20:262–271. https://doi.org/10.1038/s41556-017-0030-y
Soon CF, Khaghani SA, Youseffi M et al (2013) Interfacial study of cell adhesion to liquid crystals using widefield surface plasmon resonance microscopy. Colloids Surf, B 110:156–162. https://doi.org/10.1016/j.colsurfb.2013.04.012
Soon CF, Omar WIW, Berends RF et al (2014) Biophysical characteristics of cells cultured on cholesteryl ester liquid crystals. Micron 56:73–79. https://doi.org/10.1016/j.micron.2013.10.011
Tang M, Ding S, Min X et al (2016) Collagen films with stabilized liquid crystalline phases and concerns on osteoblast behaviors. Mater Sci Eng, C 58:977–985. https://doi.org/10.1016/j.msec.2015.09.058
Thakur VK, Thakur MK (2014) Processing and characterization of natural cellulose fibers/thermoset polymer composites. Carbohyd Polym 109:102–117. https://doi.org/10.1016/j.carbpol.2014.03.039
Tian M, Qu L, Zhang X et al (2014) Enhanced mechanical and thermal properties of regenerated cellulose/graphene composite fibers. Carbohyd Polym 111:456–462. https://doi.org/10.1016/j.carbpol.2014.05.016
Trichet L, Le Digabel J, Hawkins RJ et al (2012) Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness. Proc Natl Acad Sci USA 109:6933–6938. https://doi.org/10.1073/pnas.1117810109
Viale-Bouroncle S, Gosau M, Küpper K et al (2012) Rigid matrix supports osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHED). Differentiation 84:366–370. https://doi.org/10.1016/j.diff.2012.08.005
Vogel V, Sheetz M (2006) Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol 7:265–275. https://doi.org/10.1038/nrm1890
Wang LF, Shankar S, Rhim JW (2017) Properties of alginate-based films reinforced with cellulose fibers and cellulose nanowhiskers isolated from mulberry pulp. Food Hydrocolloids 63:201–208. https://doi.org/10.1016/j.foodhyd.2016.08.041
You Y, Zheng Q, Dong Y et al (2016) Matrix stiffness-mediated effects on stemness characteristics occurring in HCC cells. Oncotarget 7:32221–32231. https://doi.org/10.18632/oncotarget.8515
Zemel A, Rehfeldt F, Brown AE et al (2010) Optimal matrix rigidity for stress-fibre polarization in stem cells. Nat Phys 6:468–473. https://doi.org/10.1038/nphys1613
Zeng X, Li S (2011) Multiscale modeling and simulation of soft adhesion and contact of stem cells. J Mech Behav Biomed Mater 4:180–189. https://doi.org/10.1016/j.jmbbm.2010.06.002
Zhao J, Chen Y, Yang S et al (2016) Improving blood-compatibility via surface heparin-immobilization based on a liquid crystalline matrix. Mater Sci Eng, C 58:133–141. https://doi.org/10.1016/j.msec.2015.08.025
Zouani OF, Kalisky J, Ibarboure E, Durrieu M-C (2013) Effect of BMP-2 from matrices of different stiffnesses for the modulation of stem cell fate. Biomaterials 34:2157–2166. https://doi.org/10.1016/j.biomaterials.2012.12.007
Acknowledgements
This work was supported by National Natural Science Foundation of China (31971270, 82002286), the grant of Peak Climbing Project of Foshan Hospital of Traditional Chinese Medicine (CN) [No.202000190].
Funding
This work was supported by National Natural Science Foundation of China (31971270, 82002286), the grant of Peak Climbing Project of Foshan Hospital of Traditional Chinese Medicine (CN) [No.202000190].
Author information
Authors and Affiliations
Contributions
Mei Tu mainly contributed to the design ideas of research, while Rong Zeng and Shen Yu Yang contributed to the paper revision. The experimental method was mainly designed by Zheng Xie and Zhang Yao Ye. Zhang Yao Ye, Ming Yang Xie, Zheng Xie, Jing Yi and Ting Ting Huang collaborated to complete all experiments and data analysis. The initial draft of the paper was co-written by Zhang Yao Ye and Zheng Xie.
Corresponding author
Ethics declarations
Ethics approval
Not applicable.
Consent for publication
All authors have approved the manuscript and agree with its submission.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Xie, Z., Ye, Z.Y., Xie, M.Y. et al. Liquid crystal matrix-based viscoelastic mechanical stimulation regulates nuclear localization and osteogenic differentiation of rBMSCs. Cellulose 31, 5229–5248 (2024). https://doi.org/10.1007/s10570-024-05871-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10570-024-05871-3