Biomaterial surface energy-driven ligand assembly strongly regulates stem cell mechanosensitivity and fate on very soft substrates

Razafiarison, Tojo; Holenstein, Claude N.; Stauber, Tino; Jovic, Milan; Vertudes, Edward; Loparić, Marko; Kawecki, Maciej; Bernard, Laetitia; Silván, Unai; Snedeker, Jess G.

doi:10.1073/pnas.1704543115

Cited by 64 publications

(56 citation statements)

References 38 publications

(79 reference statements)

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“…Studies of cell behaviors on soft substrates have employed 2D systems coated with ECM components, which can act as adhesive anchors . Surface energy and phosphatidylinositol‐mediated signals have been demonstrated to promote cell spreading and focal adhesion on 2D soft substrates . Yet it remains largely unknown what the effect of dynamic cues on stem‐cell spheroids fate is within 3D soft microniches.…”

Section: Introductionmentioning

confidence: 77%

“…The mechanical interactions between the ECM–cell and cell–cell junctions play a key role in transmitting forces to cells in in vivo microenvironment, which can further regulate intracellular signaling pathways . At the cellular scale, the pericellular response can be viscoelastic, roughness, or surface energy as well as stiffness . Most of the known cues on cell physiology have been almost exclusively using static biomaterials.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

Zhang

Yang

Abali

et al. 2019

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Although mechanisms of how physical forces convert into biochemical signals are increasingly understood, it is still unknown how soft cues guide cell behavior. Herein, it is shown that the commitment and differentiation of encapsulating human mesenchymal stem cell (hMSC) spheroids in thermosensitive 3D hydrogels are simply altered by interpenetrating poly(N‐isopropylacrylamide‐co‐2‐hydroxyethyl methacrylate) (NIPAM‐HEMA) nanogel to a gelatin methacryloyl (GelMA) network. This cell‐laden hydrogel provides dynamic mechanics with covalent crosslinking coordinated reversible physical networks, which can regulate hMSCs in situ by reversibly stiffening soft niches via multicyclic temperature changes from 25 to 37 °C. The spreading of hMSC spheroids in the hydrogel is strongly dependent on myosin‐dependent traction stress with dynamic mechanical stimuli through focal adhesion kinase (FAK) signaling. Notably, the dynamic microenvironment gradually influences the expression and distribution from the basal to apical side of nuclear lamin A/C and increases the Yes‐associated protein (YAP) nuclear localization with cycles, which ultimately favors hMSCs undergoing osteogenesis (but not adipogenesis) in the soft microniche. Moreover, it is demonstrated that the viscoelastic behavior of the soft microniche can be guided by temperature through a nonlinear model. These findings highlight the central roles of the dynamic relationship between the biomechanical signals and mechanosensitive transcriptional regulators in cellular mechanosensing.

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Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

Zhang

Yang

Abali

et al. 2019

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“…Interestingly, primary human MSCs that grow on stiff silicone substrates doped with poly (dimethylsiloxane-ethylene oxide) (PEO) surfactant and have a θ value in the same range (60°), display a tendency of osteogenic differentiation (Razafiarison et al, 2016). Although the regulatory mechanism is not fully understood, a plausible explanation is the hydrophobicity-driven exposure of cell binding sites in the deposited extracellular matrix (ECM), collagen I in this case, which in turn directs the expression of focal adhesion components (Razafiarison et al, 2018).…”

Section: Wettabilitymentioning

confidence: 99%

On the biomechanical properties of osteosarcoma cells and their environment

Müller¹,

Silván²

2019

Int. J. Dev. Biol.

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Although rare among the general population, bone malignancies have a high rate of incidence among children and adolescents and are associated with high mortality rates. Osteosarcoma (also known as osteogenic sarcoma) is the most frequent primary cancer of bone and shows a high tendency to metastasize to the lung. Despite the frequent use of osteosarcoma-derived cell lines in basic biomechanical research and for the evaluation of cell responses to new biomaterials, the mechanical phenotype and the differences between osteosarcoma cells and related cell types, such as mesenchymal cells, osteoblasts and osteocytes, remain largely unknown. In the present review we summarize current knowledge of the biophysical and mechanical properties of the niche of primary osteosarcomas and of the malignant cells, and discuss the impact of these features on the progression of malignancy.

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“…It has been verified that MSCs cultured on soft substrates expressed more chondrogenic marker and adipogenic marker, compared to MSCs grown on stiff substrates, [ 32 ] which may be due to the surface energy‐driven supramolecular ligands of MSCs regulating cell fate by sensing of substrate mechanical compliance. [ 33 ] The strong multidifferentiation capability of hADSCs indicated that GelMA MS is an excellent vehicle for expansion of MSCs, preserving the basic properties of cells.…”

Section: Figurementioning

confidence: 99%

“All‐in‐One” Gel System for Whole Procedure of Stem‐Cell Amplification and Tissue Engineering

Liao

Zhang

et al. 2020

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Mesenchymal stem cells (MSCs) are the most favored cell type presently due to their pleiotropic properties including selfrenewal ability, multidifferentiation potential, and immunoregulation. [1] Adipose-derived mesenchymal stem cells (ADSCs) are frequently used MSCs in clinical trials because of their relative accessibility and widespread ethical acceptability. [2] However, the requirement of cell doses for per treatment commonly Microsphere (MS)-based systems provides great advantages for cell expansion and transplantation due to their high surface-to-volume ratio and biomimetic environment. However, a MS-based system that includes cell attachment, proliferation, passage, harvest, cryopreservation, and tissue engineering together has not been realized yet. An "all-in-one" gel MS-based system is established for human adipose-derived mesenchymal stem cells (hADSCs), realizing real 3D culture with enhanced expansion efficiency and simplified serial cell culture operations, and construction of macrotissues with uniform cell distribution and specific function. A 3D digital light-processing technology is developed to fabricate gel MSs in an effective way. The printed MSs present a suitable environment with rough surface architecture and the mechanical properties of soft tissues, leading to high cell viability, attachment, proliferation, activity, and differentiation potential. Further, convenient standard operation procedures, including cell passage, detachment, and cryopreservation, are established for cell culture on the gel MSs. Finally, hADSCs-loaded gel MSs form macrotissues through a "bottom-up" approach, which demonstrates the potential applications for tissue engineering. These findings exhibit the feasibility and beauty of "allin-one" stem cell culture and tissue engineering system.

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Biomaterial surface energy-driven ligand assembly strongly regulates stem cell mechanosensitivity and fate on very soft substrates

Cited by 64 publications

References 38 publications

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

On the biomechanical properties of osteosarcoma cells and their environment

“All‐in‐One” Gel System for Whole Procedure of Stem‐Cell Amplification and Tissue Engineering

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