CMCB Life Sciences Seminar: Prof. Dr. Michael Krieg, ICFO - The Institute of Photonic Sciences, Neurophotonics and Mechanical Systems Biology, Barcelona, Spain

Host: Anna Taubenberger (BIOTEC)

Title: "Mechanical compartmentalization of cellular function."

Abstract: Mechanotransduction is the process of converting a mechanical stimulus into a biochemical one, but little is understood about the molecular and mechanical pathways underlying the cellular response to force. Specifically, measuring and visualizing how mechanical stresses distribute within a cell and eventually activate cellular mechanoreceptors is still a formidable technical challenge. Over the last decade, we have developed and deployed an interdisciplinary toolbox composed of optical tweezers, force-FRET tension sensors and microfluidic devices to study the neuronal response of individual animals to defined mechanical forces. During this talk, I will describe recent strategies to democratize methods for intracellular force and mechanics measurements and highlight some of our current effort to understand neuronal mechanotransduction during touch and proprioception. Using Caenorhabditis elegans as a model, we show that MEC-2/Stomatin, an essential component of the mechanoelectrical transduction apparatus, forms biomolecular condensates that ensue from liquid-liquid phase separation and undergo a viscoelastic maturation from liquid-like to solid-like condensates. We uncovered that this phase transition is promoted by the SH3 domain of UNC-89/Titin/Obscurin through a direct interaction with MEC-2. Our data suggest a physiological role for the two phases: the naive, liquid phase facilitates transport along axons with varying caliper while the rigid condensates engage in force transfer and mechanotransduction, respectively. Together, our data demonstrate a novel function for liquid-solid phase transition in force transmission and a previously unidentified role for Titin homologs in neurons.