The challenge
The communication of cells with their environment is critical in the comprehension of the intracellular processes, and this field of study has been particularly dynamic in cell and cancer biology. Presently, available matrices to examine those interactions have tunable mechanical properties. However, the extracellular matrix (ECM) in different organ tissues and cellular settings has strikingly different chemical properties, like charge, ionic strength, ECM ligands and pH. Presently available substrates do not provide both the mechanical and biochemical tuneability required to reconstruct cancer tissues.
The solution
Manchester BIOGEL provides peptide hydrogels, PeptiGels® with tunable stiffness between 1 and 20 kPa and pH (7.4 and 6.0), thus simulating a range between healthy and cancer tissues for both characteristics. This chance to modulate mechanical and biochemical properties at the same time produces an exceptional variety of applications in mechanobiology and cancer.
The science
The majority of solid carcinomas, like pancreatic ductal adenocarcinoma (PDAC), are characterized by the development of a considerable volume of fibrous or connective tissue around the tumor that inhibits drug delivery, controls the growth and spread of tumors and controls their resistance to chemotherapy. This fibrous, acidic, tissue impacts the behavior of cancer cells from their ability to survive and proliferate.
We were excited to use Manchester BIOGELS PeptiGels® as a platform for cell biology studies and essentially tailor the hydrogel properties to mimic the mechanical and chemical environment of both healthy and cancer tissue. We went onto explore independently the influence of each on cell activation, survival and growth and are now investigating details mechanotransduction on signalling pathways.
Dr Armando Del Rio Hernandez, Department of Bioengineering, Imperial College London
The results
Images depict immunofluorescent staining of Pancreatic Adenocarcinoma Suit-2 cell line cultured on gamma 2 (soft, healthy tissue mimicking) and alpha 2 (stiff, tumor mimicking) peptide gels with low (6.0) and normal (7.4) pH.
Image Credit: Manchester BIOGEL
Stiff and acidic (tumor imitating peptide gels) induce a biomechanical response in Pancreatic Ductal Adenocarcinoma suit-2 cells that leads to an increase in proliferation (Ki67 marker – white arrows illustrate increased expression).
The future
PeptiGel® matrices opens up the possibility of exploring details of mechanotransduction signaling pathways concerned in cancer cell survival and activation.
About Manchester BIOGEL
Over 15 years ago, Professors Aline Miller and Alberto Saiani at The University of Manchester synthesised a self-assembling oligo-peptide with interesting gelation properties. This work started with a small grant from the University.
Over subsequent years, the team meticulously crafted and studied self-assembling peptides to perfect their platform technology and produce a range of hydrogels ideal for 3D cell culture. In 2014, due to a demand for their materials, our company, Manchester BIOGEL was founded to enable these hydrogels to be readily available to researchers wishing to create new opportunities in the high-growth fields of 3D cell culture, 3D bioprinting and medical devices. Since opening our doors, we have supported scientists in the UK and beyond to create optimal environments for a wide variety of cell types.
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