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Emerging Concepts in Ion Channel Biophysics
Wednesday Speaker Abstracts
14
Magnetic Force Probing of Mechanically-activated Piezo Ion Channels
Jorg Grandl
.
Duke University, Durham, NC, USA.
In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers
of an excitatory mechanically activated current found in many cells. This discovery has opened
the floodgates for studying a vast number of mechanotransduction processes. Over the past
years, groundbreaking research has identified Piezos as ion channels that sense light touch,
proprioception, and vascular blood flow, ruled out roles for Piezos in several other
mechanotransduction processes, and revealed the basic structural and functional properties of the
channel. However, many aspects of Piezo function remain mysterious, including how Piezos
convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and
what molecules and mechanisms modulate Piezo function.
We asked what specific parts (domains) of Piezo channels sense mechanical stimulation. To
probe Piezos with sub-molecular resolution we developed a novel approach where we label
specific domains within Piezos with magnetic nanoparticles and use an external magnetic field to
generate a precise mechanical force that is highly localized within the channel protein.
Simultaneously, we measure Piezo activation electrophysiologically. These experiments
identified two distinct domains as being mechanically sensitive and involved in channel
inactivation and activation.