Identification of a mechanogenetic link between substrate stiffness and chemotherapeutic response in breast cancer

Medina, Scott H.; Bush, Brian G.; Cam, Maggie; Sevcik, Emily N.; DelRio, Frank W.; Nandy, Kaustav; Schneider, Joel P.

doi:10.1016/j.biomaterials.2019.02.018

Cited by 52 publications

(32 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Links between cell resistance to treatment and mechanical stimuli have been highlighted recently. 69,83,84 Such mechanical cues could hence lead to new therapeutic approaches 85 that could be tested using such systems.…”

Section: Resultsmentioning

confidence: 99%

A new agarose-based microsystem to investigate cell response to prolonged confinement

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

A new agarose-based microsystem to investigate cell response to prolonged confinement

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Cells are sensitive to the mechanical properties of the extracellular matrix (ECM) in both physiological and pathological conditions (such as stroke, brain trauma, spinal cord injuries, cartilage damage, and tumors) [3][4][5]; it is becoming increasingly clear that the mechanical properties of the ECM are critical in directing cell fate, homeostasis, and survival [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Cross-Linked Self-Assembling Peptides and Their Post-Assembly Functionalization via One-Pot and In Situ Gelation System

Pugliese

Gelain

2020

IJMS

View full text Add to dashboard Cite

Supramolecular nanostructures formed through peptide self-assembly can have a wide range of applications in the biomedical landscape. However, they often lose biomechanical properties at low mechanical stress due to the non-covalent interactions working in the self-assembling process. Herein, we report the design of cross-linked self-assembling peptide hydrogels using a one-pot in situ gelation system, based on 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide/N-hydroxysulfosuccinimide (EDC/sulfo–NHS) coupling, to tune its biomechanics. EDC/sulfo–NHS coupling led to limited changes in storage modulus (from 0.9 to 2 kPa), but it significantly increased both the strain (from 6% to 60%) and failure stress (from 19 to 35 Pa) of peptide hydrogel without impairing the spontaneous formation of β-sheet-containing nano-filaments. Furthermore, EDC/sulfo–NHS cross-linking bestowed self-healing and thixotropic properties to the peptide hydrogel. Lastly, we demonstrated that this strategy can be used to incorporate bioactive functional motifs after self-assembly on pre-formed nanostructures by functionalizing an Ac-LDLKLDLKLDLK-CONH2 (LDLK12) self-assembling peptide with the phage display-derived KLPGWSG peptide involved in the modulation of neural stem cell proliferation and differentiation. The incorporation of a functional motif did not alter the peptide’s secondary structure and its mechanical properties. The work reported here offers new tools to both fine tune the mechanical properties of and tailor the biomimetic properties of self-assembling peptide hydrogels while retaining their nanostructures, which is useful for tissue engineering and regenerative medicine applications.

show abstract

“…Stiffness is a well-known regulator of breast cancer cell behavior. ECM stiffness leads to profound changes in cancer cell growth, metastatic potential, as well as chemotherapeutic responses [ 30 ]. Collagen crosslinking also increases the ECM stiffness, and thus promotes tumor metastasis [ 31 ].…”

Section: Extracellular Matrix In Breast Cancermentioning

confidence: 99%

The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment

2020

View full text Add to dashboard Cite

Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in maintaining homeostasis, and in the breast TME, they serve as the key components that facilitate tumor progression and immune evasion. Extracellular vesicles (EVs), the mediators that convey messages between the cells and their microenvironment through signaling molecules, have just started to capture attention in breast cancer research. In this comprehensive review, we first provide an overview of the impact of ECM in breast cancer progression as well as the alterations occurring in the TME during this process. The critical importance of EVs and their biomolecular contents in breast cancer progression and metastasis are also discussed. Finally, we discuss the potential biomedical or clinical applications of these extracellular components, as well as how they impact treatment outcomes.

show abstract

Identification of a mechanogenetic link between substrate stiffness and chemotherapeutic response in breast cancer

Cited by 52 publications

References 50 publications

A new agarose-based microsystem to investigate cell response to prolonged confinement

A new agarose-based microsystem to investigate cell response to prolonged confinement

Cross-Linked Self-Assembling Peptides and Their Post-Assembly Functionalization via One-Pot and In Situ Gelation System

The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment

Contact Info

Product

Resources

About