Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Monday Speaker Abstracts

MEMBRANE CURVATURE INITIATED MECHANOTRANSDUCTION IN CELLS Bianxiao Cui ; 1 Stanford University, Chemistry, Stanford, CA, USA Membrane curvature in the range of tens to hundreds of nanometers is involved in many essential cellular processes. At the cell-matrix interface, where the cells make physical contact with extracellular matrices, the membrane may be locally deformed by matrix topography or mechanical forces, and this deformation may actively regulate signal transmission through the interface. We explore nanofabrication to engineer vertical nanostructures protruding from a flat surface. These nanostructures deform the plasma membrane to precisely manipulate the location, degree, and sign (positive or negative) of the interface curvature in live cells. We found that these membrane curvatures significantly affect the distribution of curvature-sensitive proteins and modulate mechanotransduction in live cells. Our studies show a strong interplay between membrane curvature and mechanotransduction and reveal molecular mechanisms underlying the connection. MULTIPLE PATHWAYS OF MECHANOELECTRICAL TRANSDUCTION IN MELANOMA CELLS Kate Poole 1 ; Amrutha Patkunarajah 1 ; Surabhi Shrestha 1 ; Georgina Sanderson 1 ; Lioba Schroeter 1 ; 1 University of New South Wales, EMBL Australia Node in Single Molecule Science, School of Medical Sciences, Sydney, Australia The conversion of mechanical inputs into an electrical signal is an ancient sense, with mechanically gated channels found in all classes of life. The discovery of the PIEZO family of mechanically gated channels has had a profound impact on our understanding mechanoelectrical transduction in mammalian physiology. However, there are still substantial gaps in knowledge about how other molecules influence and mediate mechanoelectrical transduction in mammalian systems. We have recently described a PIEZO1-independent mechanoelectrical transduction pathway that depends on TMEM87a/ELKIN1 and our data suggest that ELKIN1-dependent currents can be mechanically evoked in the cell-substrate and cell-cell interfaces. Deletion of ELKIN1 from melanoma cells was found to modulate cell attachment strengths, cell mechanics, migration speeds and invasive properties, in more than one melanoma cell line. In addition, the impact of deleting ELKIN1 was found to be distinct from the impact of deleting PIEZO1 in a melanoma cell line expressing both molecules. Further work is required to clarify if ELKIN1 is modulating a mechanically activated ion channel or functioning as an ion channel itself. However, our data demonstrate that mechanoelectrical transduction in melanoma cells is not solely dependent on the PIEZO proteins and that signalling via distinct mechanoelectrical transduction pathways can result in different functional outcomes.

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