Validation of a novel device for real-time, long-term measurement of cellular forces

Projektbeschreibung

Zellmechanik mit fortgeschrittener Bildgebung revolutionär erforschen

Es ist bekannt, dass Zellen mithilfe biochemischer Signale kommunizieren, aber die Forschung hat die entscheidende Rolle mechanischer Kräfte im Zusammenhang mit Entwicklung, Physiologie und Krankheit aufgedeckt. Biologische Zellen üben Kräfte auf ihre Umgebung aus, wobei sie Schlüsselprozesse wie die Gewebebildung, die Wundheilung und das Eindringen von Krebszellen beeinflussen. Diese Kräfte zu verstehen, ist von zentraler Bedeutung. Mithilfe der vorhandenen bildgebenden Verfahren sind diese Kräfte jedoch nicht mit der erforderlichen Empfindlichkeit und Auflösung erfassbar. In diesem Zusammenhang führt das Team des ERC-finanzierten Projekts CELL-FORCE eine spezielle Interferenzmikroskopie, die Elastic Resonator Interference Stress Microscopy (ERISM), zur direkten und zerstörungsfreien Bildgebung zellulärer Kräfte ein. Sie gestattet die präzise Messung selbst schwacher Kräfte sowie eine langfristige, lichtschadenfreie Abbildung der Zelldynamik. Hier besteht das Potenzial, die Erforschung der Zellbiomechanik, die Wirkstoffentwicklung und die Diagnostik zu revolutionieren.

Ziel

The conventional thinking in cell biology, which often assumes that cells communicate mostly via bio-chemical signalling, has recently been challenged with several examples where mechanical rather than chemical cues play an important role in development, physiology and disease. Biological cells continually exert forces on their environment, which can vary substantially in magnitude, spatial distribution and temporal evolution. These forces are key to many processes including cell growth, tissue formation, wound healing and the invasion of cancer cells into healthy tissue. Understanding how cellular forces affect the micro-environment hinges on our ability to image them with sufficient local and temporal resolution (e.g. continuously over several days with subcellular spatial resolution), adequate field of view (e.g. to study cell sheets) and relevant sensitivity (typical forces are in the pico to nano Newton range). Despite significant advances made in this area of functional bioimaging over the last years, existing methods still struggle to meet the requirements, thus precluding new commercial opportunities in cell biomechanics. CELL-FORCE will demonstrate Elastic Resonator Interference Stress Microscopy (ERISM) as a new microscopy method that allows direct, robust and non-destructive imaging of forces associated with various mechanical cell-substrate interactions, and validate its commercial feasibility. The greatly increased sensitivity offered by ERISM over other methods allows for accurate measurements of vertical forces and of cells exerting only weak force. Moreover, with a low light intensity requirement and no need to detach cells after a measurement, using ERISM makes it possible to take long-term measurements of multiple cells without photodamage and facilitates downstream applications such as immunostaining. This will open up new commercial opportunities in fundamental research, drug development and (long-term) in diagnostics.