Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro

Ashworth, J.; Thompson, Juliette; James, Jenna Rebekah; Slater, Charlotte E; Pijuan-Galito, Sara; Lis-Slimak, Katarzyna; Holley, Rebecca; Meade, Kate; Thompson, Alexander; Arkill, Kenton P.; Tassieri, Manlio; Wright, Amanda J.; Farnie, Gilian; Merry, Catherine L.R.

doi:10.1016/j.matbio.2019.06.009

Cited by 52 publications

(52 citation statements)

References 48 publications

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“…[ 49 ] Due to good biocompatibility, presumable biodegradability, flexible adaptability, high bioavailability, and predictive bioactive capability to interact with tissue or cells, designer self‐assembling peptide hydrogels have been developed to form an advanced type of hydrogels for the prominent advantages to deeply study cell–ECM interactions or stem cell fates in 3D cell cultures in vitro. [ 9a,64 ] Furthermore, designer self‐assembling peptide scaffolds may be designed to realize extensive biological functionality of hydrogel matrices, such as the desired physicochemical properties, desirable mechanical stiffness and possible biological cues for cell growth in vitro, including customizing the inherent native interactions of cells with ECM, and its consequent in situ microtissue remodeling. [ 9b,64,65 ] So, choosing designer self‐assembling peptide hydrogel to culture cells for 3D tissue remodeling in vitro, it is possible to better emulate the physiology of their original ECM in specific tissue types.…”

Section: Common Hydrogel Products and Biomedical Featuresmentioning

confidence: 99%

“…[ 9a,64 ] Furthermore, designer self‐assembling peptide scaffolds may be designed to realize extensive biological functionality of hydrogel matrices, such as the desired physicochemical properties, desirable mechanical stiffness and possible biological cues for cell growth in vitro, including customizing the inherent native interactions of cells with ECM, and its consequent in situ microtissue remodeling. [ 9b,64,65 ] So, choosing designer self‐assembling peptide hydrogel to culture cells for 3D tissue remodeling in vitro, it is possible to better emulate the physiology of their original ECM in specific tissue types. Compared with various natural hydrogels and synthetic polymer hydrogels (Table 1), in designer self‐assembling peptide hydrogels, dipeptides, tripeptides, tetrapeptide, and their many times repeated peptide sequences are exciting hierarchical main building blocks for various subset of hydrogels, which surely represent biological or inspired candidate motifs to realize molecular bioengineering assembly strategy for precise 3D tissue reconstructs in vitro.…”

Section: Common Hydrogel Products and Biomedical Featuresmentioning

confidence: 99%

“…The functionalized EFK‐RGD peptide hydrogel independently controls the matrix stiffness and cell binding site concentration to influence cell spreading and differentiation within the nanofibrous 3D hydrogel matrix. [ 107 ] To avoid lot to lot variability and compositional or manufactural complexity in probing cell–cell and cell–ECM interactions, [ 64 ] EFK8 peptide hydrogel combined with fully defined matrix components provides a reliable and reproducible type of 3D cell culture models with independent control of the biochemical and mechanical properties in the extracellular microenvironments in vitro. So, in 3D cell cultures, EFK8 peptide hydrogel may control independently the critical factors: matrix composition and bulk stiffness, which are the key aspects to model the tumor progression from normal breast to breast cancer, including the study of specific cancer cell behaviors.…”

Section: Diverse Self‐assembling Peptide Hydrogels and Their Applicatmentioning

confidence: 99%

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Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Yang

Zhao

2020

Advanced Science

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mouse intestinal stem cells and primary colorectal cancer cells can be propagated in vitro long term, [1] there is an urgent need to develop more physiologically relevant, efficient, and robust precise oncology models that closely recapitulate the genetic and morphological heterogeneous composition and mimic the arrangement pattern of cancer cells in the original tumor. [2] To our knowledge in biomedical research, hydrogel is the best tool to reconstruct precise oncology models in vitro, especially tumor organoid, which not only recapitulates in vivo biology and microenvironmental factors, but also at large extent allows side-by-side comparison to evaluate the translational potential of 3D model systems to the patients. [2a,3] Generally, hydrogels are mainly composed of hydrophilic polymeric scaffolds that absorb large amounts of water, so the hydrogel matrix better mimics elastic and viscoelastic properties in ECM and microscale topographies of cell matrices, which controls proper cell morphology, directs viable cell behaviors, and drives in vivo fundamental cell-cell or cell-ECM interactions. [4] To recapitulate pathophysiological features of human tumors and imitate various aspects of human tumorigenesis in vivo, hydrogels can provide a realistic platform to establish a useful bridge between in vitro assays and in vivo cell microenvironments. In current biomedical applications, there are many kinds of hydrogels to be developed to mimic the biological properties of ECM, such Designer self-assembling peptides form the entangled nanofiber networks in hydrogels by ionic-complementary self-assembly. This type of hydrogel has realistic biological and physiochemical properties to serve as biomimetic extracellular matrix (ECM) for biomedical applications. The advantages and benefits are distinct from natural hydrogels and other synthetic or semisynthetic hydrogels. Designer peptides provide diverse alternatives of main building blocks to form various functional nanostructures. The entangled nanofiber networks permit essential compositional complexity and heterogeneity of engineering cell microenvironments in comparison with other hydrogels, which may reconstruct the tumor microenvironments (TMEs) in 3D cell cultures and tissue-specific modeling in vitro. Either ovarian cancer progression or recurrence and relapse are involved in the multifaceted TMEs in addition to mesothelial cells, fibroblasts, endothelial cells, pericytes, immune cells, adipocytes, and the ECM. Based on the progress in common hydrogel products, this work focuses on the diverse designer self-assembling peptide hydrogels for instructive cell constructs in tissue-specific modeling and the precise oncology remodeling for ovarian cancer, which are issued by several research aspects in a 3D context. The advantages and significance of designer peptide hydrogels are discussed, and some common approaches and coming challenges are also addressed in current complex tumor diseases.

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Section: Common Hydrogel Products and Biomedical Featuresmentioning

confidence: 99%

Section: Common Hydrogel Products and Biomedical Featuresmentioning

confidence: 99%

Section: Diverse Self‐assembling Peptide Hydrogels and Their Applicatmentioning

confidence: 99%

See 1 more Smart Citation

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Yang

Zhao

2020

Advanced Science

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“…Ashworth and colleagues have described a self-assembling peptide gel that can be customized with further matrix components if desired, and levels of stiffness modified through a strictly controlled gelation process. (18) The initial formation of a matrix-free precursor is achieved using a commercially available peptide gelator containing phenylalanine, glutamic acid, and lysine, the concentrations of which dictate the overall stiffness of the matrix product. Homogeneity within the gel matrix is ensured by first reverting to a liquid state brought about by the manipulation of pH and temperature (heated to 80 C); after which, cells and other organic components can be added.…”

Section: Culture Model Systemsmentioning

confidence: 99%

“…The use of synthetic matrices offers the potential to overcome such obstacles through the creation of cellular environments tailored to the specific in vivo characteristics being modeled. Ashworth and colleagues have described a self‐assembling peptide gel that can be customized with further matrix components if desired, and levels of stiffness modified through a strictly controlled gelation process . The initial formation of a matrix‐free precursor is achieved using a commercially available peptide gelator containing phenylalanine, glutamic acid, and lysine, the concentrations of which dictate the overall stiffness of the matrix product.…”

Section: Introductionmentioning

confidence: 99%

Modeling the Human Bone–Tumor Niche: Reducing and Replacing the Need for Animal Data

Rao

Edwards

2020

JBMR Plus

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Bone is the most common site for cancer metastasis. Understanding the interactions within the complex, heterogeneous bone–tumor microenvironment is essential for the development of new therapeutics. Various animal models of tumor‐induced bone disease are routinely used to provide valuable information on the relationship between cancer cells and the skeleton. However, new model systems exist that offer an alternative approach to the use of animals and might more accurately reveal the cellular interactions occurring within the human bone–tumor niche. This review highlights replacement models that mimic the bone microenvironment and where cancer metastases and tumor growth might be assessed alongside bone turnover. Such culture models include the use of calcified regions of animal tissue and scaffolds made from bone mineral hydroxyapatite, synthetic polymers that can be manipulated during manufacture to create structures resembling trabecular bone surfaces, gel composites that can be modified for stiffness and porosity to resemble conditions in the tumor–bone microenvironment. Possibly the most accurate model system involves the use of fresh human bone samples, which can be cultured ex vivo in the presence of human tumor cells and demonstrate similar cancer cell–bone cell interactions as described in vivo. In addition, the use of mathematical modeling and computational biology approaches provide an alternative to preliminary animal testing. The use of such models offers the capacity to mimic significant elements of the human bone–tumor environment, and complement, refine, or replace the use of preclinical models. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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What Caging Force Cells Feel in 3D Hydrogels: A Rheological Perspective

Ciccone

Dobre

Gibson

et al. 2020

Adv Healthcare Materials

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It has been established that the mechanical properties of hydrogels control the fate of (stem) cells. However, despite its importance, a one‐to‐one correspondence between gels' stiffness and cell behavior is still missing from literature. In this work, the viscoelastic properties of poly(ethylene‐glycol) (PEG)‐based hydrogels are investigated by means of rheological measurements performed at different length scales. The outcomes of this work reveal that PEG‐based hydrogels show significant stiffening when subjected to a compressional deformation, implying that conventional bulk rheology measurements may overestimate the stiffness of hydrogels by up to an order of magnitude. It is hypothesized that this apparent stiffening is caused by an induced “tensional state” of the gel network, due to the application of a compressional normal force during sample loading. Moreover, it is shown that the actual stiffness of the hydrogels is instead accurately determined by means of both passive‐video‐particle‐tracking (PVPT) microrheology and nanoindentation measurements, which are inherently performed at the cell's length scale and in absence of any externally applied force in the case of PVPT. These results underpin a methodology for measuring hydrogels' linear viscoelastic properties that are representative of the mechanical constraints perceived by cells in 3D hydrogel cultures.

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Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro

Cited by 52 publications

References 48 publications

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Modeling the Human Bone–Tumor Niche: Reducing and Replacing the Need for Animal Data

What Caging Force Cells Feel in 3D Hydrogels: A Rheological Perspective

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