3D Cell Cultures unlock revolutionary insights in Tissue Mechanics
A team of researchers at the University of Gottingen in Germany have recently developed a 3D cell culture chamber that allows them to culture tissue samples that mimic mechanical conditions in disease. With this new technology, researchers and drug developers may be able to accurately measure the effects of drugs on tissues without using experimental animals, solving ethical dilemmas and time constraints. A recent grant from the European Union to the team is helping them further develop this technology, which they are working to make available for clinical use as soon as possible.
3D cell chambers for biomedical research
Researchers at the University of Gottingen, Germany, have recently devised a new 3D culture chamber for culturing tissue samples to study their mechanical properties. Typically, culture chambers only allow researchers to measure the biological and chemical properties of cells, tissues, and biochemical substances. To understand mechanical properties, researchers had to utilize experimental animals or observe human patients, which is expensive, complex, and fraught with ethical dilemmas. This new technology can extend the utility of tissue culture to include investigations of mechanical properties.
According to Professor Timo Betz, the head of Betz Labs in Gottingen, the new research project aims to develop a system that allows automated screening of the effects of new drugs on human tissue. In his words, this “also means that scientists will be able to model different health conditions in the lab to get a better understanding of disease processes and treatments. This could be a game changer for the pharmaceutical industry as well as academic and medical research.”
The mechanical investigations that the new technology will potentially enable range from monitoring drug actions to mimicking the mechanical changes that tissues experience in disease states, which is particularly helpful for tissues such as skeletal muscle, cardiac (heart) muscle, and smooth muscle. The chamber includes elastic posts to which the muscle fibres can attach and pull so that researchers can measure the tensile strength of the muscle’s activity. The activity of muscle fibres and proteins such as collagen, actin, and myosin can be significantly altered in disease states, and measuring the level of contractility is essential for monitoring disease progression and evaluating recovery or management.
For example, dystrophin and sarcoglycans in muscular dystrophy are significantly disrupted within the dystrophin protein complex. In typical muscle architecture, the dystrophin complex is abundant in myofibres, where it is concentrated into costameres, which are rib-like structures in the plasma membrane. Where dystrophin is absent, the plasma membrane shows increased fragility, reduced stiffness, and increased leakiness, initiating a cascade that results in tissue necrosis. In sarcopenia, an ageing-associated disease of the skeletal muscles, there may be significant dysregulation of the myostatin, c-Jun NH2-terminal kinase, and the Akt signalling pathways.
Understanding these pathways is critical for making valid diagnoses and developing viable solutions to these conditions. For example, a 2010 paper revealed that testosterone supplementation reversed sarcopenia by regulating the myostatin, c-Jun NH2-terminal kinase, Akt, and Notch signalling pathways, improving its applicability in managing muscle loss in ageing. The new 3D cell culture, which Betz and his team are currently developing, has the potential to make such discoveries faster and more accessible to researchers in the relevant biotechnology fields.
3D Cell Culture can help researchers quantify mechanical activity
Professor Betz and his team first revealed their findings about the utility of 3D cell culture in a paper published in Methods in Cell Biology in January 2015. In the article titled ‘Quantification of collagen contraction in three-dimensional cell culture,’ the researchers outline how they used a 3D culture to measure the flow dynamics of collagen contraction using a pseudo-speckle technique. Noting that various cells, such as fibroblasts (cells of connective tissue such as the dermis of the skin), endothelial cells, smooth muscle cells, and cancer cells, exert traction on the extracellular matrix, the researchers sought to observe matrix contraction in tissue models.
The team successfully observed and quantified local contraction at the micron scale, measured the direction and speed of contractions, and observed useful parameters in cell invasions, gene expression, wound healing, and cancer metastasis. The image analysis was presented using in-house software developed in the Matlab programming environment.
TissMec & 3D Cell Culture: A valuable new reality
Professor Timo Betz, the lead researcher on this project, completed his PhD in 2007 at the Soft Matter Physics Division of the University of Leipzig. Shortly after, he accepted a postdoc position in Cécile Sykes’ soft matter research group at the Institut Curie in Paris. He attained a professorship at the University of Münster in 2016, where he studied the physics of soft tissues in tumours, often using tissue cultures in high-impact studies. Betz moved to Gottingen in 2020, where he leads the Betz Lab to study how mechanics is involved in the interaction between various biological components.
Among his team of researchers at Betz Lab are Bart Vos, a postdoc at Gottingen; Fatemeh Abbasi, a PhD student at Gottingen; Matthias Brandt, a PhD student at the University of Munster; Mohammad Amin Eskandari, a PhD student at Gottingen, and Hendrik Schürmann, an MD candidate at Munster. Other members of his team are Mahboubeh Farajian, a PhD student at Gottingen, Arne Hofemeier, a PhD student at Munster, and Alejandro Jurado. The team’s research has focused on deciphering fundamental physical processes in living cells to develop better health outcomes.
To accelerate the team’s work on 3D cell culture, Prof Timo Betz was recently awarded a Proof of Concept (PoC) grant from the European Research Council to further develop his 3D screening system to cultivate tissue and simulate its mechanical properties. The project, called TissMec, also aims to allow researchers to measure the properties of tissues in 3D automatically. The European Research Council’s PoC grants provide top-up funding of €150,000 over 18 months to selected researchers to build on their findings to create new technologies and innovation. The enhanced laboratory version the team is developing can allow scientists to mimic mechanical situations in severe conditions such as cardiovascular disease or muscular dystrophy. This can significantly improve its use in medical research and the development of new therapies.
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