Forces have a profound role across all living systems, and many processes ranging from development and migration to mitosis and meiosis cannot proceed without precisely tuned mechanical signals. A major challenge to understanding chemo-mechanical couplings in biology pertains to the lack of molecular tools that allow one to image and manipulate forces within cells and especially at the cell membrane. To address this issue, we have developed a set of fluorescent probes and molecular opto-actuators to investigate the role of mechanical forces in biochemical signaling. In this talk, I will first describe the synthesis and characterization of molecular force probes and their application in the area of mechanotransduction. Force probes take advantage of fluorescence quenching to determine the extension of an entropic polymer �spring� to quantify tension using a standard fluorescence microscope (Nat. Methods 2012). I will describe the development of second and third generation force probes that allow one to quantify molecular forces with high spatial and temporal resolution for a range of recombinant proteins. Finally, I will discuss the development of molecular tension actuators and their application to studying Notch and integrin receptor mechano-regulation in living systems. 

Visualizing and manipulating forces in the membrane of living cells

247th National Meeting (2014)

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