Within tissues, cells are embedded in complex, three-dimensional structures known as the extracellular matrix. Their biomechanical interactions play a crucial role in numerous biological processes. Scientists at the Max Planck Institute for the Science of Light (MPL) have now developed a novel lab-on-a-chip system based on intelligent hydrogel structures, which enables precise pressure forces to be applied to cellular microenvironments. The recently presented method could find future applications in medical diagnostics for mechanical disorders in living tissues.
Biomechanics of cells simulated in lab-on-a-chip method
The mechanical remodeling of the extracellular microenvironment plays a crucial role in biological processes such as the development and maintenance of physiological equilibrium (homeostasis) and wound healing. Replicating this in the laboratory can provide insights into the causes of pathological changes. However, previous instrumental methods could not be integrated into lab-on-a-chip systems and offered only limited accuracy. The team led by Dr. Katja Zieske, head of the independent research group "Molecular Biophysics & Living Matter" at MPL, now presents a new method which can be used to simulate spatially and temporally controlled mechanical perturbations of biological polymer networks on a lab-on-a-chip system. Biological processes occurring during such perturbations can thus be examined microscopically.
Intelligent hydrogels as micromachines
The scientists use intelligent hydrogel microstructures. These powerful materials consist of polymers which respond to stimuli such as light or temperature by changing their structure. Depending on the stimulus, they contract or expand. The researchers at MPL took advantage of these properties to exert specifically defined biomechanical forces on biological polymer networks such as collagen. In addition, scientists were able to evaluate the compatibility of the system with living cells.
First, Zieske's team produced and optimized thermoresponsive hydrogel microstructures in flow chambers. The expansion of the hydrogel microstructures was tested under time-controlled temperature stimulation to compress various molecular networks, such as Matrigel, a gel-like protein mixture, and a collagen network. After compression, the associated deformation was measured. While Matrigel deformed plastically, collagen relaxed elastically. By mimicking cellular pressure forces using intelligent hydrogel microstructures, Zieske's team has developed a new, versatile system for research purposes. Future studies may focus on the remodeling of the extracellular matrix as well as the effects of mechanical forces on its cellular microenvironment, both in physiological and pathological contexts.
"Our method allows us to generate mechanical forces with high spatial and temporal precision, and to record their effects on biological systems. In collagen, we were able to detect changes triggered by these forces even at distances of hundreds of micrometers by tracking fluorescent microspheres," says Vicente Salas-Quiroz, first author of the presented work.
"Our vision is to develop smart microstructures for medical diagnostics in order to contribute to a sustainable healthcare system – for example, in the investigation of 3D cell model systems such as cancer models and models for blood vessel formation. Intelligent hydrogel microstructures in lab-on-a-chip systems could serve as micromachines in the future to manipulate tissue models on the micrometer scale. We see great potential here for diagnostic use," adds Zieske.
