Biofunctional supramolecular hydrogels fabricated from a short self-assembling peptide modified with bioactive sequences for the 3D culture of breast cancer MCF-7 cells

Chia, Jyh Yea; Miki, Takayuki; Mihara, Hisakazu; Tsutsumi, Hiroshi

doi:10.1016/j.bmc.2021.116345

Cited by 8 publications

(6 citation statements)

References 41 publications

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“…It was also observed that with similar hydrogel stiffness, cells embedded in hydrogels containing RGD proliferated more, according to the lower fluorescence intensity, than no RGD hydrogels made from the same polymer concentration (Figure S10b,c). These results point to the role of RGD in promoting the proliferation of MCF-7 cells in a 3D hydrogel environment, consistent with previous studies, that show hydrogel with RGD adhesive peptide effectively promotes the proliferation of endothelial cells. − …”

Section: Resultssupporting

confidence: 91%

Electrostatic Assembly of Multiarm PEG-Based Hydrogels as Extracellular Matrix Mimics: Cell Response in the Presence and Absence of RGD Cell Adhesive Ligands

Suwannakot

Nemec

Peres

et al. 2023

ACS Biomater. Sci. Eng.

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Synthetic hydrogels have been used widely as extracellular matrix (ECM) mimics due to the ability to control and mimic physical and biochemical cues observed in natural ECM proteins such as collagen, laminin, and fibronectin. Most synthetic hydrogels are formed via covalent bonding resulting in slow gelation which is incompatible with drop-on-demand 3D bioprinting of cells and injectable hydrogels for therapeutic delivery. Herein, we developed an electrostatically crosslinked PEG-based hydrogel system for creating high-throughput 3D in vitro models using synthetic hydrogels to mimic the ECM cancer environment. A 3-arm PEG-based polymer backbone was first modified with either permanent cationic charged moieties (2-(methacryloyloxy)ethyl trimethylammonium) or permanent anionic charged moieties (3-sulfopropyl methacrylate potassium salt). The resulting charged polymers can be conjugated further with various amounts of cell adhesive RGD motifs (0, 25, 75, and 98%) to study the influences of RGD motifs on breast cancer (MCF-7) spheroid formation. Formation, stability, and mechanical properties of hydrogels were tested with, and without, RGD to evaluate the cellular response to material parameters in a 3D environment. The hydrogels can be degraded in the presence of salts at room temperature by breaking the interaction of oppositely charged polymer chains. MCF-7 cells could be released with high viability through brief exposure to NaCl solution. Flow cytometry characterization demonstrated that embedded MCF-7 cells proliferate better in a softer (60 Pa) 3D hydrogel environment compared to those that are stiffer (1160 Pa). As the stiffness increases, the RGD motif plays a role in promoting cell proliferation in the stiffer hydrogel. Flow cytometry characterization demonstrated that embedded MCF-7 cells proliferate better in a softer (60 Pa) 3D hydrogel environment compared to those that are stiffer (1160 Pa). As the stiffness increases, the RGD motif plays a role in promoting cell proliferation in the stiffer hydrogel. Additionally, cell viability was not impacted by the tested hydrogel stiffness range between 60 to 1160 Pa. Taken together, this PEG-based tuneable hydrogel system shows great promise as a 3D ECM mimic of cancer extracellular environments with controllable biophysical and biochemical properties. The ease of gelation and dissolution through salt concentration provides a way to quickly harvest cells for further analysis at any given time of interest without compromising cell viability.

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Section: Resultssupporting

confidence: 91%

Electrostatic Assembly of Multiarm PEG-Based Hydrogels as Extracellular Matrix Mimics: Cell Response in the Presence and Absence of RGD Cell Adhesive Ligands

Suwannakot

Nemec

Peres

et al. 2023

ACS Biomater. Sci. Eng.

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“…While several previous studies have shown spheroid culture, 24,58 the formation of spheroids in supramolecular nanofibrillar hydrogels, 46,47 and pre-made spheroid fusion in supramolecular hydrogels with a vicosus component, 59,60 the influence of hydrogel viscoelasticity on cell aggregation/spheroid formation in 3D remains unknown. We further hypothesized that changes in the viscoelasticity/stress relaxation of the matrix could lead to control over cell aggretation – more simply, is this phenomena a viscoelastic timescale dependent phenomena?…”

Section: Resultsmentioning

confidence: 99%

“…37,39,40 Molecular engineering of peptide amphiphiles, 41 short peptides, 42 ureido-pyrimidinone (UPy) 43 and BTAs 36,44,45 has been employed to achieve fibrous structures and control the macroscale mechanical properties of hydrogels. Several recent reports have shown the ability for nanofibrillar hydrogels to support and facilitate cell aggregation; 46,47 however, the role of viscoelastic timescales (or network exchange) on the speed or amount of cell aggregation has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Modular mixing of benzene-1,3,5-tricarboxamide supramolecular hydrogelators allows tunable biomimetic hydrogels for control of cell aggregation in 3D

et al. 2022

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“…Self-assembling amyloidogenic peptides are easily modified with biologically active ligands, including peptides, and functional amyloid-like fibrils have been used as a biomaterial [ 15 , 23 ]. The FVFYV peptide assembles itself and forms amyloid-like fibrils without cellular effects and is easily modified with functional sequences.…”

Section: Discussionmentioning

confidence: 99%

Structural Requirement of hA5G18 Peptide (DDFVFYVGGYPS) from Laminin α5 Chain for Amyloid-like Fibril Formation and Cell Adhesion

Zhang

Yamada²,

Kumai³

et al. 2022

Molecules

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The hA5G18 peptide (DDFVFYVGGYPS) identified from the human laminin α5 chain G domain promotes cell attachment and spreading when directly coated on a plastic plate, but does not show activity when it is conjugated on a chitosan matrix. Here, we focused on the structural requirement of hA5G18 for activity. hA5G18 was stained with Congo red and formed amyloid-like fibrils. A deletion analysis of hA5G18 revealed that FVFYV was a minimum active sequence for the formation of amyloid-like fibrils, but FVFYV did not promote cell attachment. Next, we designed functional fibrils using FVFYV as a template for amyloid-like fibrils. When we conjugated an integrin binding sequence Arg-Gly-Asp (RGD) to the FVFYV peptide with Gly-Gly (GG) as a spacer, FVFYVGGRGD promoted cell attachment in a plate coat assay, but a negative control sequence RGE conjugated peptide, FVFYVGGRGE, also showed activity. However, when the peptides were conjugated to Sepharose beads, the FVFYVGGRGD beads showed cell attachment activity, but the FVFYVGGRGE beads did not. These results suggest that RGD and RGE similarly contribute to cell attachment activity in amyloid-like fibrils, but only RGD contributes the activity on the Sepharose beads. Further, we conjugated a basic amino acid (Arg, Lys, and His) to the FVFYV peptide. Arg or Lys-conjugated FVFYV peptides, FVFYVGGR and FVFYVGGK, showed cell attachment activity when they were coated on a plate, but a His-conjugated FVFYV peptide FVFYVGGH did not show activity. None of the basic amino acid-conjugated peptides showed cell attachment in a Sepharose bead assay. The cell attachment and spreading on FVFYVGGR and FVFYVGGK were inhibited by an anti-integrin β1 antibody. These results suggest that the Arg and Lys residues play critical roles in the interaction with integrins in amyloid-like fibrils. FVFYV is useful to use as a template for amyloid-like fibrils and to develop multi-functional biomaterials.

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Biofunctional supramolecular hydrogels fabricated from a short self-assembling peptide modified with bioactive sequences for the 3D culture of breast cancer MCF-7 cells

Cited by 8 publications

References 41 publications

Electrostatic Assembly of Multiarm PEG-Based Hydrogels as Extracellular Matrix Mimics: Cell Response in the Presence and Absence of RGD Cell Adhesive Ligands

Electrostatic Assembly of Multiarm PEG-Based Hydrogels as Extracellular Matrix Mimics: Cell Response in the Presence and Absence of RGD Cell Adhesive Ligands

Modular mixing of benzene-1,3,5-tricarboxamide supramolecular hydrogelators allows tunable biomimetic hydrogels for control of cell aggregation in 3D

Structural Requirement of hA5G18 Peptide (DDFVFYVGGYPS) from Laminin α5 Chain for Amyloid-like Fibril Formation and Cell Adhesion

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