Research focusing on how cells communicate with their environment is crucial for a greater understanding of intracellular processes, and this field has been highly active in cancer and cell biology. Contemporary matrices that are used to investigate these interactions now contain tunable mechanical and biochemical characteristics.

The extracellular matrix (ECM) in tissues of various cellular environments and organs have highly dissimilar chemical properties, for example, in charge, ionic strength, ECM ligands, and pH. Substrates that are available at present do not provide the biochemical and mechanical tuneability that is required to mimic and reproduce cancer tissues.

PeptiGels are peptide hydrogels created by Manchester BIOGEL and critially they are fully-defined and anmial free. Interestingly their mechanical and biochemical properties are tunable which means they can be varied systematically to create scaffolds that mimic healthy and tumour tissue, as well as mimic differing stages of tumour development.For example scaffoldscan be prepared to independantly vary pH (betweenpH 7.4 and 6.0)and stiffness (between 1 and 20 kPa) which enables imitation ofthe range for cancerous and healthy tissues for both parameters.

A novel range of applications in cancer and mechanobiology can be created through the ability to modulate biochemical and mechanical properties at the same time.

The majority of solid carcinomas, for example, Pancreatic Ductal Adenocarcinoma (PDAC), are distinguished by the emergence of a large quantity of fibrous or connective tissue around the tumor, which regulates their resistance to chemotherapy, inhibits drug delivery, and controls the growth and spread of tumors.

This fibrous, acidic tissue influences cancer cell behavior in 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 signaling pathways.

Dr Armando Del Rio Hernandez, Department of Bioengineering, Imperial College London

Image Credit: Manchester BIOGEL

The images present immunofluorescent staining of a Pancreatic Adenocarcinoma Suit-2 cell line cultured on alpha 2 (stiff, tumor mimicking) and gamma 2 (healthy, soft tissue mimicking) peptide gels with normal (7.4) and low (6.0) pH.

The Pancreatic Ductal Adenocarcinoma suit-2 cells exhibit a biochemical response as a result of the stiff and acidic (tumor mimicking peptide gels), which creates an increase in proliferation (Ki67 marker where the increased expression is highlighted with white arrows).

PeptiGel matrices provide the ability to discover details of the mechanotransduction signaling pathways which influence the survival and activation of cancer cells.

The most recent results from this project, funded by Innovate KTP (KTP12102), can be found at http://biomechanicalregulation-lab.org.

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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Characterization of Pancreatic Cancer Cells Response to Peptigels that Mimic Healthy and Tumor Tissue Properties - News-Medical.net